Re: Mitochondrial Antioxidant Mitoquinone (MitoQ) May Reduce Liver Necroinflammation

[Guest guest]

Thanks , I just put in a call to my Doc regarding this. This is something that would be good for me when avaliable since my AST & ALT both have been over 250(even during treatment). I will let you know what they say about it. wrote: Mitochondrial Antioxidant Mitoquinone (MitoQ) May Reduce Liver Necroinflammation in Patients with Chronic Hepatitis C By Liz Highleyman In people with hepatitis C, oxidative stress associated with chronic viral infection is thought to be one of the mechanisms underlying liver damage, which ultimately can progress to advanced fibrosis or cirrhosis. Since only about half of all hepatitis C patients treated with pegylated interferon plus ribavirin achieve a "cure," or sustained virological response, there remains an urgent need for therapies that can slow, halt, or reverse liver

damage. At the 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008) last month in Milan, investigators reported results from a study of mitoquinone in chronic hepatitis C patients with elevated liver enzyme levels. Mitoquinone, being developed by Antipodean Pharmaceuticals, is a novel oral antioxidant that covalently bonds with coenzyme Q10, causing the antioxidant to accumulate several-hundred fold within the mitochondria (energy-producing structures within the cells) thereby protecting them from oxidative damage and apoptosis (cell death). Several in vitro and animal models of cell injury have demonstrated that mitoquinone is more potent than non-selective antioxidants in preventing apoptosis due to oxidative stress.

The researchers conducted a Phase II study to assess the effect of mitoquinone on serum aminotransferase (ALT and AST) and HCV RNA levels. In this small trial, 30 hepatitis C patients were randomly assigned to receive 40 mg or 80 mg once-daily mitoquinone or else placebo for 28 days. Participants had elevated ALT (2 to 10 x ULN) and Metavir stage F0-F2 fibrosis at baseline, and were either prior non-responders or unsuitable for interferon-based therapy. Participants were assessed at days 3, 7, 10, 14, 18, 21, and 28 during treatment, and at days 35, 42, and 56 in the post-treatment follow-up period. The last subject completed treatment in November 2007. The primary endpoint was percentage change in serum ALT from baseline to day 28. Results • Mitoquinone was well tolerated, with no serious adverse events reported. • ALT declined significantly from baseline in the mitoquinone arm, both in terms of absolute level and percentage change (P < 0.05). • The ALT decline in the mitoquinone arm was greater than in the placebo group (45 vs 9 U/L; P = 0.054). Conclusion "These results suggest that

mitoquinone may reduce necroinflammation in HCV infection," the investigators concluded. They added that, "Larger, longer duration studies are planned to determine the role of mitoquinone in prevention of fibrosis progression in patients with chronic liver disease."Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand; Department of Gastroenterology, Waikato Hospital, Hamilton, New Zealand; Antipodean Pharmaceuticals, Auckland, New Zealand; Mitochondrial Dysfunction Group, MRC Dunn Human Nutrition Unit, Cambridge, UK; Department Of Chemistry, Otago University, Dunedin, New Zealand; Department of Medicine, Otago University, Christchurch, New Zealand. Below is an edited excerpt of a recent press release from Antipodean Pharmaceuticals announcing the results presented at EASL: Antipodean Pharmaceuticals Announces Results of Phase 2 Study of Lead Compound MitoQ April 24, 2008 -- San Francisco, CA -- Antipodean Pharmaceuticals, Inc. announced today, at the European Meeting for the Study of the Liver (EASL), the positive results of a Phase 2 trial of its lead compound MitoQ (mitoquinone) in liver disease. The trial, conducted by Dr. Gane, Associate Professor of Medicine, New Zealand Liver Transplant Unit at Auckland City Hospital, successfully met the primary clinical endpoint, the reduction of elevated liver enzymes. In the 28-day trial, 30 patients with the hepatitis C virus (HCV) were enrolled to study the effects of MitoQ on elevated liver enzymes. Researchers measured patients'

baseline levels of aminotransferase (ALT), an enzyme released into the blood that indicates damage to the liver. The double-blind trial randomized patients to one of three treatment groups: MitoQ 40 mg/day, MitoQ 80 mg/day, or placebo. The primary endpoint was the reduction of levels of ALT. Patients who received MitoQ showed a significant decrease in ALT levels at the end of the study compared with baseline levels. The decrease from baseline was 26.4% (P<0.002) for patients in the 40 mg dose group, and 28% (P<0.05) for patients in the 80 mg dose group. These results suggest that MitoQ can reduce necroinflammation and may halt disease progression to fibrosis or cirrhosis. The drug was well tolerated with no significant safety issues. Commonly reported adverse events (AEs) included nausea, headache and vomiting, which were usually mild and well tolerated. Only one patient withdrew from the study due to nausea. There were no significant laboratory or

ECG abnormalities observed and no serious adverse events (SAEs) were reported. "In patients with chronic liver disease, including the two patient populations with the largest unmet need -- patients with chronic hepatitis C, who have failed current standard of care, and patients with non-alcoholic fatty liver disease (NAFLD) -- there are currently no therapeutic options available to prevent progression to cirrhosis, liver failure and liver cancer," stated Dr. Gane. "In the future, these patients may benefit from maintenance therapy with interventions such as MitoQ, which block either hepatic necroinflammation or fibrogenesis.""In the coming year, Antipodean plans to explore and develop its lead compound for the treatment of hepatological diseases, particularly non-alcoholic fatty liver disease," said Ken , PhD, Chief Executive Officer of Antipodean Pharmaceuticals. "The company is actively seeking to achieve this goal with the help of a

pharmaceutical partner."A 12-month study in patients in Parkinson's disease showed MitoQ to be well tolerated; however, there was no significant effect on disease progression. Dr. Barry Snow, Department of Neurology, Auckland Hospital, New Zealand, and Principal Investigator of the trial of MitoQ in Parkinson's disease, believes that the lack of efficacy in Parkinson's Disease may have been due to the large number of impaired cells in that disease; these cells may have had limited or no ability to regenerate, and thus could not benefit from MitoQ's antioxidant properties. The company believes MitoQ has therapeutic potential in diseases where cell regeneration occurs, such as hepatological and dermatological disorders.About MitoQMitoQ is a mitochondria-targeted antioxidant that selectively blocks mitochondrial oxidative damage and prevents liver cell apoptosis. MitoQ is based on a novel technology,

targeted lipophilic cations that transport and concentrate antioxidants into the mitochondria -- organelles inside cells that provide energy for life processes -- where they accumulate up to a thousand fold. Targeted antioxidants can reduce the hepatic oxidative damage that is induced by viral infection and that is also involved in the progression of NAFLD through to NASH, leading to fibrosis or cirrhosis.About Antipodean Antipodean is a clinical-stage pharmaceutical company developing targeted molecules that prevent oxidative damage to endothelial, epithelial and liver cells leading to apoptosis and fibrosis. The company is developing a mitochondria-targeted antioxidant, MitoQ (mitoquinone mesylate), for the treatment of hepatic inflammatory disorders caused by oxidative stress such as nonalcoholic fatty liver disease (NAFLD) and

nonalcoholic steatohepatitis (NASH). The company's business plan is to develop drugs to the point of proof of principle and then partner further development. Antipodean has research collaborations with pre-clinical and clinical investigators in Cambridge, U.K., Auckland, New Zealand, and several centers in the U.S. to identify and develop lead compounds through to clinical proof-of-principle. Currently the Company's lead compounds target liver and skin diseases. Antipodean is located in San Francisco, California.

[Guest guest]

Your doctor will not have access to this stuff unless he is a researcher also . What is published is years away from being approved by the fda .

Re: Mitochondrial Antioxidant Mitoquinone (MitoQ) May Reduce Liver Necroinflammation

Thanks ,

I just put in a call to my Doc regarding this. This is something that would be good for me when avaliable since my AST & ALT both have been over 250(even during treatment). I will let you know what they say about it.

<elizabethnv1earthlink (DOT) net> wrote:

Mitochondrial Antioxidant Mitoquinone (MitoQ) May Reduce Liver Necroinflammation in Patients with Chronic Hepatitis C By Liz Highleyman

In people with hepatitis C, oxidative stress associated with chronic viral infection is thought to be one of the mechanisms underlying liver damage, which ultimately can progress to advanced fibrosis or cirrhosis.

Since only about half of all hepatitis C patients treated with pegylated interferon plus ribavirin achieve a "cure," or sustained virological response, there remains an urgent need for therapies that can slow, halt, or reverse liver damage.

At the 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008) last month in Milan, investigators reported results from a study of mitoquinone in chronic hepatitis C patients with elevated liver enzyme levels.

Mitoquinone, being developed by Antipodean Pharmaceuticals, is a novel oral antioxidant that covalently bonds with coenzyme Q10, causing the antioxidant to accumulate several-hundred fold within the mitochondria (energy-producing structures within the cells) thereby protecting them from oxidative damage and apoptosis (cell death). Several in vitro and animal models of cell injury have demonstrated that mitoquinone is more potent than non-selective antioxidants in preventing apoptosis due to oxidative stress.

The researchers conducted a Phase II study to assess the effect of mitoquinone on serum aminotransferase (ALT and AST) and HCV RNA levels. In this small trial, 30 hepatitis C patients were randomly assigned to receive 40 mg or 80 mg once-daily mitoquinone or else placebo for 28 days. Participants had elevated ALT (2 to 10 x ULN) and Metavir stage F0-F2 fibrosis at baseline, and were either prior non-responders or unsuitable for interferon-based therapy.

Participants were assessed at days 3, 7, 10, 14, 18, 21, and 28 during treatment, and at days 35, 42, and 56 in the post-treatment follow-up period. The last subject completed treatment in November 2007. The primary endpoint was percentage change in serum ALT from baseline to day 28.

Results

• Mitoquinone was well tolerated, with no serious adverse events reported. • ALT declined significantly from baseline in the mitoquinone arm, both in terms of absolute level and percentage change (P < 0.05). • The ALT decline in the mitoquinone arm was greater than in the placebo group (45 vs 9 U/L; P = 0.054).

Conclusion

"These results suggest that mitoquinone may reduce necroinflammation in HCV infection," the investigators concluded.

They added that, "Larger, longer duration studies are planned to determine the role of mitoquinone in prevention of fibrosis progression in patients with chronic liver disease."Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand; Department of Gastroenterology, Waikato Hospital, Hamilton, New Zealand; Antipodean Pharmaceuticals, Auckland, New Zealand; Mitochondrial Dysfunction Group, MRC Dunn Human Nutrition Unit, Cambridge, UK; Department Of Chemistry, Otago University, Dunedin, New Zealand; Department of Medicine, Otago University, Christchurch, New Zealand.

Below is an edited excerpt of a recent press release from Antipodean Pharmaceuticals announcing the results presented at EASL:

Antipodean Pharmaceuticals Announces Results of Phase 2 Study of Lead Compound MitoQ

April 24, 2008 -- San Francisco, CA -- Antipodean Pharmaceuticals, Inc. announced today, at the European Meeting for the Study of the Liver (EASL), the positive results of a Phase 2 trial of its lead compound MitoQ (mitoquinone) in liver disease. The trial, conducted by Dr. Gane, Associate Professor of Medicine, New Zealand Liver Transplant Unit at Auckland City Hospital, successfully met the primary clinical endpoint, the reduction of elevated liver enzymes. In the 28-day trial, 30 patients with the hepatitis C virus (HCV) were enrolled to study the effects of MitoQ on elevated liver enzymes. Researchers measured patients' baseline levels of aminotransferase (ALT), an enzyme released into the blood that indicates damage to the liver. The double-blind trial randomized patients to one of three treatment groups: MitoQ 40 mg/day, MitoQ 80 mg/day, or placebo. The primary endpoint was the reduction of levels of ALT. Patients who received MitoQ showed a significant decrease in ALT levels at the end of the study compared with baseline levels. The decrease from baseline was 26.4% (P<0.002) for patients in the 40 mg dose group, and 28% (P<0.05) for patients in the 80 mg dose group. These results suggest that MitoQ can reduce necroinflammation and may halt disease progression to fibrosis or cirrhosis. The drug was well tolerated with no significant safety issues. Commonly reported adverse events (AEs) included nausea, headache and vomiting, which were usually mild and well tolerated. Only one patient withdrew from the study due to nausea. There were no significant laboratory or ECG abnormalities observed and no serious adverse events (SAEs) were reported. "In patients with chronic liver disease, including the two patient populations with the largest unmet need -- patients with chronic hepatitis C, who have failed current standard of care, and patients with non-alcoholic fatty liver disease (NAFLD) -- there are currently no therapeutic options available to prevent progression to cirrhosis, liver failure and liver cancer," stated Dr. Gane. "In the future, these patients may benefit from maintenance therapy with interventions such as MitoQ, which block either hepatic necroinflammation or fibrogenesis.""In the coming year, Antipodean plans to explore and develop its lead compound for the treatment of hepatological diseases, particularly non-alcoholic fatty liver disease," said Ken , PhD, Chief Executive Officer of Antipodean Pharmaceuticals. "The company is actively seeking to achieve this goal with the help of a pharmaceutical partner."A 12-month study in patients in Parkinson's disease showed MitoQ to be well tolerated; however, there was no significant effect on disease progression. Dr. Barry Snow, Department of Neurology, Auckland Hospital, New Zealand, and Principal Investigator of the trial of MitoQ in Parkinson's disease, believes that the lack of efficacy in Parkinson's Disease may have been due to the large number of impaired cells in that disease; these cells may have had limited or no ability to regenerate, and thus could not benefit from MitoQ's antioxidant properties. The company believes MitoQ has therapeutic potential in diseases where cell regeneration occurs, such as hepatological and dermatological disorders.About MitoQMitoQ is a mitochondria-targeted antioxidant that selectively blocks mitochondrial oxidative damage and prevents liver cell apoptosis. MitoQ is based on a novel technology, targeted lipophilic cations that transport and concentrate antioxidants into the mitochondria -- organelles inside cells that provide energy for life processes -- where they accumulate up to a thousand fold. Targeted antioxidants can reduce the hepatic oxidative damage that is induced by viral infection and that is also involved in the progression of NAFLD through to NASH, leading to fibrosis or cirrhosis.About Antipodean

Antipodean is a clinical-stage pharmaceutical company developing targeted molecules that prevent oxidative damage to endothelial, epithelial and liver cells leading to apoptosis and fibrosis. The company is developing a mitochondria-targeted antioxidant, MitoQ (mitoquinone mesylate), for the treatment of hepatic inflammatory disorders caused by oxidative stress such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). The company's business plan is to develop drugs to the point of proof of principle and then partner further development. Antipodean has research collaborations with pre-clinical and clinical investigators in Cambridge, U.K., Auckland, New Zealand, and several centers in the U.S. to identify and develop lead compounds through to clinical proof-of-principle. Currently the Company's lead compounds target liver and skin diseases. Antipodean is located in San Francisco, California.

[Guest guest]

Steph's doctors are at a teaching hospital, you can bet they are up on all of it, I only wish I were close enough to go there..elizabethnv1 wrote: Your doctor will not have access to this stuff unless he is a researcher also . What is published is years away from being approved by the fda . Re: Mitochondrial Antioxidant Mitoquinone (MitoQ) May Reduce Liver Necroinflammation Thanks , I just put in a call to my Doc regarding this. This is something that would be good for me when avaliable since my AST & ALT both have been over 250(even during treatment). I will let you know what they say about it. <elizabethnv1earthlink (DOT) net> wrote: Mitochondrial Antioxidant Mitoquinone (MitoQ) May Reduce Liver Necroinflammation in Patients with Chronic Hepatitis C By Liz Highleyman In people with hepatitis C, oxidative stress associated with chronic viral infection is thought to be one of the mechanisms underlying liver damage, which ultimately can progress to advanced fibrosis or cirrhosis. Since only about half of all hepatitis C patients treated with pegylated interferon plus ribavirin achieve a "cure," or sustained virological response, there remains an urgent need for therapies that can slow, halt, or reverse liver damage. At the 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008) last month in Milan, investigators reported results from a study of mitoquinone in chronic hepatitis C patients with elevated liver enzyme levels. Mitoquinone, being developed by Antipodean Pharmaceuticals, is a novel

oral antioxidant that covalently bonds with coenzyme Q10, causing the antioxidant to accumulate several-hundred fold within the mitochondria (energy-producing structures within the cells) thereby protecting them from oxidative damage and apoptosis (cell death). Several in vitro and animal models of cell injury have demonstrated that mitoquinone is more potent than non-selective antioxidants in preventing apoptosis due to oxidative stress. The researchers conducted a Phase II study to assess the effect of mitoquinone on serum aminotransferase (ALT and AST) and HCV RNA levels. In this small trial, 30 hepatitis C patients were randomly assigned to receive 40 mg or 80 mg once-daily mitoquinone or else placebo for 28 days. Participants had elevated ALT (2 to 10 x ULN) and Metavir stage F0-F2 fibrosis at baseline, and were either prior non-responders or unsuitable for interferon-based therapy.

Participants were assessed at days 3, 7, 10, 14, 18, 21, and 28 during treatment, and at days 35, 42, and 56 in the post-treatment follow-up period. The last subject completed treatment in November 2007. The primary endpoint was percentage change in serum ALT from baseline to day 28. Results • Mitoquinone was well tolerated, with no serious adverse events reported. • ALT declined significantly from baseline in the mitoquinone arm, both in terms of absolute level and percentage change (P < 0.05). • The ALT decline in the mitoquinone arm was greater than in the placebo group (45 vs 9 U/L; P = 0.054). Conclusion "These results suggest that mitoquinone may reduce necroinflammation in HCV infection," the investigators concluded. They added that, "Larger, longer duration studies are planned to determine the role of mitoquinone in prevention of fibrosis progression in patients with chronic liver disease."Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand; Department of Gastroenterology, Waikato Hospital,

Hamilton, New Zealand; Antipodean Pharmaceuticals, Auckland, New Zealand; Mitochondrial Dysfunction Group, MRC Dunn Human Nutrition Unit, Cambridge, UK; Department Of Chemistry, Otago University, Dunedin, New Zealand; Department of Medicine, Otago University, Christchurch, New Zealand. Below is an edited excerpt of a recent press release from Antipodean Pharmaceuticals announcing the results presented at EASL: Antipodean Pharmaceuticals Announces Results of Phase 2 Study of Lead Compound MitoQ April 24, 2008 -- San Francisco, CA -- Antipodean Pharmaceuticals, Inc. announced today, at the European Meeting for the Study of the Liver

(EASL), the positive results of a Phase 2 trial of its lead compound MitoQ (mitoquinone) in liver disease. The trial, conducted by Dr. Gane, Associate Professor of Medicine, New Zealand Liver Transplant Unit at Auckland City Hospital, successfully met the primary clinical endpoint, the reduction of elevated liver enzymes. In the 28-day trial, 30 patients with the hepatitis C virus (HCV) were enrolled to study the effects of MitoQ on elevated liver enzymes. Researchers measured patients' baseline levels of aminotransferase (ALT), an enzyme released into the blood that indicates damage to the liver. The double-blind trial randomized patients to one of three treatment groups: MitoQ 40 mg/day, MitoQ 80 mg/day, or placebo. The primary endpoint was the reduction of levels of ALT. Patients who received MitoQ showed a significant decrease in ALT levels at the end of the study compared with baseline levels. The decrease from baseline was 26.4% (P<0.002)

for patients in the 40 mg dose group, and 28% (P<0.05) for patients in the 80 mg dose group. These results suggest that MitoQ can reduce necroinflammation and may halt disease progression to fibrosis or cirrhosis. The drug was well tolerated with no significant safety issues. Commonly reported adverse events (AEs) included nausea, headache and vomiting, which were usually mild and well tolerated. Only one patient withdrew from the study due to nausea. There were no significant laboratory or ECG abnormalities observed and no serious adverse events (SAEs) were reported. "In patients with chronic liver disease, including the two patient populations with the largest unmet need -- patients with chronic hepatitis C, who have failed current standard of care, and patients with non-alcoholic fatty liver disease (NAFLD) -- there are currently no therapeutic options available to prevent progression to cirrhosis, liver failure and liver cancer," stated Dr. Gane. "In

the future, these patients may benefit from maintenance therapy with interventions such as MitoQ, which block either hepatic necroinflammation or fibrogenesis.""In the coming year, Antipodean plans to explore and develop its lead compound for the treatment of hepatological diseases, particularly non-alcoholic fatty liver disease," said Ken , PhD, Chief Executive Officer of Antipodean Pharmaceuticals. "The company is actively seeking to achieve this goal with the help of a pharmaceutical partner."A 12-month study in patients in Parkinson's disease showed MitoQ to be well tolerated; however, there was no significant effect on disease progression. Dr. Barry Snow, Department of Neurology, Auckland Hospital, New Zealand, and Principal Investigator of the trial of MitoQ in Parkinson's disease, believes that the lack of efficacy in Parkinson's Disease may have been due to the large number of impaired cells in that disease; these cells may have had

limited or no ability to regenerate, and thus could not benefit from MitoQ's antioxidant properties. The company believes MitoQ has therapeutic potential in diseases where cell regeneration occurs, such as hepatological and dermatological disorders.About MitoQMitoQ is a mitochondria-targeted antioxidant that selectively blocks mitochondrial oxidative damage and prevents liver cell apoptosis. MitoQ is based on a novel technology, targeted lipophilic cations that transport and concentrate antioxidants into the mitochondria -- organelles inside cells that provide energy for life processes -- where they accumulate up to a thousand fold. Targeted antioxidants can reduce the hepatic oxidative damage that is induced by viral infection and that is also involved in the progression of NAFLD through to NASH, leading to fibrosis or cirrhosis.About Antipodean Antipodean is a clinical-stage pharmaceutical company developing targeted molecules that prevent oxidative damage to endothelial, epithelial and liver cells leading to apoptosis and fibrosis. The company is developing a mitochondria-targeted antioxidant, MitoQ (mitoquinone mesylate), for the treatment of hepatic inflammatory disorders caused by oxidative stress such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). The company's business plan is to develop drugs to the point of proof of principle and then partner further development. Antipodean has research collaborations with pre-clinical and clinical investigators in Cambridge, U.K., Auckland, New Zealand, and several centers in the U.S. to identify and develop lead compounds through to clinical proof-of-principle. Currently the Company's lead compounds target liver and skin diseases. Antipodean is located in San

Francisco, California.