New long-acting local anesthetic derived from algae effectively blocks pain in s

[Guest guest]

New long-acting local anesthetic derived from algae effectively blocks pain in

surgical patients

Children's Hospital Boston to collaborate with Chilean start-up to conduct US

preclinical and clinical studies

http://www.eurekalert.org/pub_releases/2011-02/chb-nll022311.php

Boston, MA -- A U.S.-Chile collaboration is bringing surgical patients closer to

having a long-acting local anesthetic. In a randomized, double-blind trial,

patients given neosaxitoxin, a new local anesthetic derived from algae, had

significantly less postoperative pain and recovered about two days sooner than

those given the commonly used local anesthetic bupivacaine. Based on this

finding, Children's Hospital Boston, a co-investigator on the study, has signed

a collaboration agreement with biotech start-up company Proteus SA (Santiago,

Chile) to move the new anesthetic toward clinical adoption.

Tens of millions of patients have operations requiring local anesthesia each

year. Current local anesthetics act for less than 8 hours; when they wear off,

patients generally need opioid analgesics, which cause substantial side effects,

including nausea, sedation, shallow breathing, sleepiness, constipation and

itching. These side effects often delay recovery and can result in prolonged

hospitalization.

Neosaxitoxin (neoSTX) provides local anesthesia for more than 24 hours. It is a

site 1 sodium-channel blocker, part of a larger class of emerging anesthetics

based on molecules derived from aquatic organisms.

" In my opinion, there has not been a truly innovative new local anesthetic

medication in the last 40 to 50 years, " notes study coauthor Berde, MD,

PhD, chief of the Division of Pain Medicine at Children's Hospital Boston. " Most

drugs introduced over that time period have represented only minimal advances.

There have been candidate drugs that went in novel directions, but they've had

shortcomings, and none have made it to market. "

The neoSTX trial, the first of its kind, involved 137 Chilean patients having

laparoscopic removal of their gall bladders. As reported in the March-April

issue of Regional Anesthesia and Pain Medicine, significantly fewer patients

randomized to neoSTX reported severe postoperative pain at the incision site at

both 12 hours (4 vs. 18 percent) and 24 hours (6 vs. 16 percent). Significantly

more neoSTX-treated patients had complete absence of pain at 12 hours, both at

rest (88 vs. 69 percent) and with movement (80 vs. 60 percent). Patients in the

neoSTX group reported a full functional recovery approximately 2 days earlier.

No serious adverse reactions occurred in either group.

The trial was a three-part effort led by first author Alberto Rodríguez-Navarro,

MD, at Padre Hurtado Hospital (Santiago, Chile); a clinical-academic team led by

Berde; and a pharmaceutical development team led by Novoa, CEO of Proteus

SA. " As a surgeon who specializes in abdominal surgery, I think that the future

of pain treatment will benefit greatly from this type of multidisciplinary

collaboration, " says Rodríguez-Navarro.

The Chilean and American investigators met through their scientific

publications. Berde and Kohane, MD, PhD, a clinician-researcher in

Critical Care Medicine at Children's, had studied site 1 sodium-channel blockers

derived from marine toxins for more than a decade. Their work in rats showed

that the compounds lack the side effects of existing anesthetics and opioid

analgesics. They are not addictive, have no cardiac toxicity and don't cross the

blood-brain barrier, thus avoiding the risk of seizures occasionally seen with

existing local anesthetics. They also cause minimal local tissue reaction,

avoiding the nerve and muscle damage seen with high concentrations of existing

local anesthetics.

Meanwhile, in Chile, Rodríguez-Navarro had published work examining the

anesthetic potential of neoSTX, derived from local algae.

The scientists at Proteus have developed expertise in extracting, culturing and

purifying large amounts of neoSTX from freshwater microalgae, and formulating

the compound for medical use. The planned clinical studies at Children's, hoped

to begin this year, will look for optimal doses that block pain while avoiding

toxicity.

Groups of young adult volunteers will receive neoSTX injections under the skin

in gradually increasing doses. Although NeoSTX has appeared very safe in over

400 patients in clinical trials so far, the upcoming study will more precisely

determine the margin of safety. Subjects will be closely monitored for numbness

at the injection sites, as well as whole-body effects.

The team believes that even more prolonged local anesthesia is possible. They

have data from animals and exploratory studies in humans showing that combining

Site-1 sodium channel blockers with existing local anesthetics can produce nerve

blockade for up to 2 to 4 days – with minimal local or systemic side effects.

" We think that the demand for a long-acting local anesthetic will vast, " says

Novoa of Proteus. " Our initial estimates suggest a market greater than 1 billion

dollars. "

Children's holds a U.S. patent on site 1 sodium-channel toxins as

prolonged-duration local anesthetics. The clinical trial was supported by an

Innova Corfo Project.

###

Children's Hospital Boston is home to the world's largest research enterprise

based at a pediatric medical center, where its discoveries have benefited both

children and adults since 1869. More than 1,100 scientists, including nine

members of the National Academy of Sciences, 12 members of the Institute of

Medicine and 13 members of the Medical Institute comprise

Children's research community. Founded as a 20-bed hospital for children,

Children's Hospital Boston today is a 392-bed comprehensive center for pediatric

and adolescent health care grounded in the values of excellence in patient care

and sensitivity to the complex needs and diversity of children and families.

Children's also is the primary pediatric teaching affiliate of Harvard Medical

School. For more information about research and clinical innovation at Boston

Children's, visit its Vector blog.