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Page 82 Rosales et al. J Transl Genet Genom 2020;4:81-90 I https://doi.org/10.20517/jtgg.2020.12

outcome of NAMDC. The grant selection process is facilitated by input from multiple stakeholders including
patient organizations and the strategic leadership of NAMDC. To train new mitochondrial disease investigators,
NAMDC has established a Fellowship Program which offers a unique training opportunity to senior postdoctoral
clinical fellows. The fellowship includes a 6-month period of intensive training in clinical trial methodology through
the Clinical Research Enhancement through Supplemental Training program and equivalent programs at the other
sites, along with rotations up to 3 months each to two additional consortium sites where a rich and varied training
experience is provided. Nine core educational sites participate in this training program, each offering a summer
grant program in mitochondrial medicine funded by our NAMDC partner the United Mitochondrial Disease
Foundation (www.umdf.org). All clinical research in NAMDC depends on the participation of mitochondrial
disease patients. Since individual mitochondrial disorders are often extremely rare, major communication and
recruitment efforts are required. Therefore, NAMDC has forged a very close partnership with the premier patient
advocacy group for mitochondrial diseases in North America, the United Mitochondrial Disease Foundation
(UMDF).

Results: The NAMDC Registry has confirmed the clinical and genetical heterogeneity of mitochondrial diseases
due to primary mutations in mitochondrial DNA or nuclear DNA. During the 8 years of this NIH-U54 grant, this
consortium, acting in close collaboration with a patient advocacy group, the UMDF, has effectively addressed
these complex diseases. NAMDC has expanded a powerful patient registry with more than 1600 patients enrolled
to date, a website for education and recruitment of patients (www.namdc.org), a NAMDC biorepository housed
at the Mayo Clinic in Rochester, MN, and essential diagnostic guidelines for consensus research. In addition,
eight clinical studies have been initiated and the NAMDC fellowship program has been actively training the next
generation of mitochondrial disease clinical investigators, of which six have completed the program and remain
actively involved in mitochondrial disease research.

Conclusion: The NAMDC Patient Registry and Biorepository is actively facilitating mitochondrial disease research,
and accelerating progress in the understanding and treatment of mitochondrial diseases.

Keywords: Mitochondrial disease, registry, consortium, rare disease

INTRODUCTION
Mitochondrial diseases due to OxPhos defects and caused by mutations in either the mitochondrial or
the nuclear genome are an exceptionally heterogeneous group of disorders. Some are confined to the
central or peripheral nervous system (encephalopathy, peripheral neuropathy, and myopathy) but most are
multisystemic. Although clinical severity varies, often within families or within cohorts of patients harboring
the same pathogenic mutation, by and large these are progressive and often crippling disorders, causing
weakness, exercise intolerance, fatigue, ataxia, seizures, mental retardation, dementia, hearing loss, blindness,
parkinsonism, strokes, peripheral neuropathies, and premature death. Because of the clinical heterogeneity
and the frequent multisystemic involvement, mitochondrial diseases present formidable diagnostic
challenges. When accurately diagnosed, they pose even more formidable therapeutic difficulties, as there are
very few disease-modifying therapies, and symptomatic therapies, often only anecdotally reported, and are
only partially effective.

There is a vibrant international research community engaged in the study of the mechanisms and clinical
characterization of mitochondrial diseases and the search for better treatments. However, since there is a
large number of distinct mitochondrial diseases, each with relatively low incidence, it has been difficult to
assemble sufficiently large datasets or patient groups for research studies and clinical trials.