Bill...interesting about LGMD (and really MD in general)

[Guest guest]

Was just reading through the LGMD question and answer page and found this

and thought it was interesting. Funny too because I had just been

sitting here wondering if the CPK level would drop in anyone even if the

cause was NOT one of the inflammatory myopathy's....seems like that is

the case atleast some of the time.

That inflammatory cells can be found in other types of MD, and that

pred can and does lower their muscle enzyme numbers was of particular interest.

Got me thinking.......considering there are a number of MD's where the

CK levels stay consistently elevated, just makes me wonder why the urgency

exists in trying to bring those numbers down in PM/DM. I realize

that the enzymes indicate muscle breaking down, and that it is important

to try and make that stop, just thought it interesting that it does not

seem to be as "big a deal" when it comes to other types of MD. I

might be reading something into the abstracts and such that I read, and

maybe if there was something that they knew would bring the enzymes down

in other forms of MD there would be more urgency afterall. Just an

interesting thing to ponder!!

BIG hugs,

Can steroids help an individual with LGMD? Also, have any studies or tests

been done regarding steroids and

LGMD?

REPLY from MDA: Marcy C. Speer, Ph.D., Duke University Medical Center,

Durham

First, I am assuming when the term, steroids, is used, it is not referring

to anabolic steroids which have been

used (illegally) by individuals to improve athletic performance. This occurs

because of increased muscle mass

which these drugs may produce as a side effect. This is not the indication

that the drug was approved for, but one

of many potential side effects, some of which are life threatening. In

their present formulation these drugs are in no

way appropriate to be used as a treatment for LGMD or any muscle disease.

I therefore assume you are referring

to the glucocorticoid, prednisone. This is an anti- inflammatory drug which

has been utilized in the treatment of two

of the muscular dystrophies: selected patients with facioscapulohumeral(FSH)

syndrome and a number of patients

with Duchenne muscular dystrophy (DMD). Four patients with a clinical syndrome

of FSH MD were treated with

prednisone because there was evidence of inflammatory cells on their

muscle biopsies. The rationale for treatment

was that prednisone has successfully treated true inflammatory diseases

of muscle (e.g., polymyositis) in which

inflammatory cells are also present in significant amount in muscle biopsies.

Theodore Munsat and his colleagues

[1] reported that three of their patients showed clinical improvement and

a significant lowering of their muscle

enzymes. Their enzymes became abnormal again when prednisone was stopped.

A fourth patient likewise had

normalization of his muscle enzymes after treatment, but no clinical improvement.

There were no control patients in

this treatment trial, however. The authors hypothesized that certain patients

with the clinical syndrome of FSH have

a phase early in the disease process in which inflammation is part of the

pathologic process. During this time this

group of patients might benefit from steroids.

Patients with DMD have been treated with prednisone in a number of studies

over the years. Trials were

carried out in a randomized, double blinded fashion involving multiple

centers from 1989 through the present.

Although these studies have documented enhanced muscle strength and function,

it has not been maintained for

longer than three years at which time steroid side effects became prominent.

Additionally, the exact mechanism by

which prednisone produces the reported benefits is unknown. Several explanations

have been postulated, however,

such as inhibition of the breakdown of muscle protein (rather than stimulating

protein production) [2],

anti-inflammation [3],but not immunosuppression [4], and muscle fiber alterations

and increased steroid receptors

[3].

The difficulty in addressing the question of steroids and LGMD is threefold.

To date there have been no

controlled clinical trials utilizing prednisone in LGMD so there is nothing

to base an opinion on. Second,

prednisone is not a drug without prominent potential side effects. Thus,

it would be necessary to have a rationale

for why a medication that is an anti-inflammatory would be of benefit in

LGMD before embarking on a clinical

trial. Third, LGMD is a heterogeneous grouping of diseases which have varying

modes of inheritance, varying

chromosomal locations, and varying protein products (e.g., selected sarcoglycans

and calpain-3). All individuals in

a treatment trial would have to be genetically classified as to their protein

defects since these differences could

result in differing responses to a treatment.

References: