Almost 1 year ago, the first patient with multiple system atrophy (MSA) was enrolled in the clinical trial with sirolimus. The trial, a phase 2 placebo-controlled study, is currently being conducted at the NYU Dysautonomia Center only and is sponsored by the NIH. The goal of the study is to determine if sirolimus is of sufficient promise to slow the progression of MSA, a disorder characterized by the abnormal accumulation of the protein alpha-synuclein in the brain and that, so far, has no cure.

The rationale to use sirolimus is supported by two facts: first, sirolimus (also known as rapamycin) has been FDA-approved for several decades now, to treat disorders other than MSA, namely to prevent organ transplant rejection. Because sirolimus has been around for a while, the profile of adverse events and potential interactions with other drugs is very well known.

And second, when mouse models of neurodegenerative diseases, including those caused by alpha-synuclein, were treated with sirolimus, the rate of neurodegeneration and the burden of alpha-synuclein deposition diminished. The evidence is animal models is very strong and, as a consequence, sirolimus has been since posited as a potential treatment for neurodegenerative diseases (https://www.ncbi.nlm.nih.gov/pubmed/21772323).

Taken together, all this imply that sirolimus might be useful to treat patients with MSA. With these encouraging facts, NIH reviewed, approved, and provided oversight and funding for the trial at NYU.

Some numbers

The first patient was enrolled and randomized in September 2018. This was the first time ever that sirolimus was being used in an attempt to slow the progression of a neurodegenerative disease. So far, 41 patients from all over the U.S. have been enrolled and randomized. Four have completed the trial, which has a duration of 1 year. This has been an outstanding rate of recruitment, which indicates the high interest that this trial has generated among the MSA community.

Was the drug effective in those 4 patients that have already completed the trial?

This is not known yet, as the trial is blinded, meaning, some patients received sirolimus and some others received placebo. We won’t be able to tell if the drug had any effect until all patients complete the trial, which is when the blinding will be eliminated and we will be able to know who was taking what, which will allow statistics. This is how all placebo-controlled trials work.

Is the drug safe? What are its most common side effects?

The consent form of the clinical trial summarizes the potential side effects of the drug. Among the patients that are or have been enrolled in the trial, common adverse events included mild diarrhea, swollen ankles, and mouth sores. Needless to say, because the study is blinded we don’t know if these side effects are directly due to the sirolimus, or if they occurred in patients taking placebo.

Can I still participate in the sirolimus trial?

Yes, the trial is still open for recruitment and a few spots are still available. Please, call the NYU Dysautonomia Center – 212 263 7225 if you would like more information about the trial.

I do not live in New York City. Can I still participate in the sirolimus trial?

Yes, the trial has some funds to compensate for travel expenses for patients coming from out of New York. We want to facilitate that as many patients as possible can participate in the trial without a significant impact in their personal finances.

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More info: Lee-Ann Lugg (Lee-Ann.Lugg@nyulangone.org), NYU Dysautonomia Center, 530 First Avenue, Suite 9Q, New York, NY 10016, Tel: +1 212 263 7225