PROJECT SUMMARY/ABSTRACT:
Facioscapulohumeral muscular dystrophy (FSHD) is the second most common adult muscular dystrophy in the
world with a global prevalence of ~4:100,000. Clinically, patients with FSHD experience progressive
weakness, muscle wasting, and varied symptomatic burden. As adult patients with FSHD age, they frequently
develop difficulty walking or lose the ability to ambulate due to profound weakness and muscle atrophy.
Currently, there are no therapies that have been demonstrated to reverse or even slow the progressive
symptoms associated with FSHD. A treatment that limits disease progression and/or reverses functional
decline would be beneficial to this population. In 2022, we successfully completed a single center (University
of Rochester), single-arm, proof-of-concept study to evaluate the safety and tolerability of daily rHGH
(Genotropin®) combined with testosterone enanthate injections every 2 weeks in men with FSHD. Participants
received study drugs for 24 weeks followed by a 12-week washout period. Participants received serial safety
testing, laboratory testing, functional assessments, and disease burden monitoring during the study with no
participants experiencing a serious adverse event. After 24 weeks, the six-minute walk distance increased by
37.3 meters (p=0.001), lean body mass improved by 2.2 kg (p<0.0001), body fat reduced by 1.3 kg (p=0.044),
overall strength (standardized QMT, average % of predicted normal) increased by 3% (p=0.033), clinical
function (FSHD-COM) improved by 12% (2.4 points; p=0.006), and total disease burden (FSHD-HI) reduced by
19% (6 points; p=0.043) from baseline. While this approach generated one of the largest gains of function in
response to a therapy in FSHD, a larger placebo-controlled efficacy study is needed to further validate these
results. The proposed one-year planning award allows for the completion of all of the preliminary steps
needed to successfully initiate and eventually conduct such a study. Planning award activities will include but
will not be limited to: 1) finalizing the study protocol, statistical analysis plan, data and safety monitoring plan,
and all required study materials; 2) securing pharmaceutical contracts for study drugs; 3) identifying and
securing partnerships with external collaborators and clinical sites; 3) initiating the IRB approval process; and,
4) applying for a NIAMS U01 clinical trial award to support the implementation and conduct of a multicenter
phase 3 study. Ultimately, this phase 3 study will evaluate an extremely promising therapeutic approach for
improving ambulation, strength, lean body mass, and symptomatic burden in a well-defined cohort of patients
with FSHD and will pave the way for FDA approval of a potentially life-improving therapy for patients with this
muscular dystrophy.
