bims-curels 2023-12-31 papers

Issue of 2023‒12‒31
three papers selected by
Cure Mito Foundation

Ther Adv Rare Dis. 2023 Jan-Dec;4:4 26330040231219272

The Rare Diseases Clinical Research Network: a model for clinical trial readiness.

Background: The current road to developing treatments for rare diseases is often slow, expensive, and riddled with risk. Change is needed to improve the process, both in how we think about rare disease treatment development and the infrastructure we build to support ongoing science. The National Institutes of Health (NIH)-supported Rare Diseases Clinical Research Network (RDCRN) was established to advance the diagnosis, management, and treatment of rare diseases and to promote highly collaborative, multi-site, patient-centric, translational, and clinical research. The current iteration of the RDCRN intends to build upon and enhance successful approaches within the network while identifying innovative methods to fill gaps and address needs in the approach to the rare disease treatment development process through innovation, collaboration, and clinical trial readiness.Objective: The objective of this paper is to provide an overview of the productivity and influence of the RDCRN since it was first established 20 years ago.
Design and methods: Using a suite of tools available to NIH staff that provides access to a comprehensive, curated, extensively linked data set of global grants, patents, publications, clinical trials, and FDA-approved drugs, a series of queries were executed that conducted bibliometric, co-author, and co-occurrence analysis.
Results: The results demonstrate that the entire RDCRN consortia and network has been highly productive since its inception. They have produced 2763 high-quality publications that have been cited more than 100,000 times, expanded international networks, and contributed scientifically to eight FDA-approved treatments for rare diseases.
Conclusion: The RDCRN program has successfully addressed some significant challenges while developing treatments for rare diseases. However, looking to the future and being agile in facing new challenges that arise as science progresses is important.

Keywords: clinical trial readiness; consortium; network; rare diseases; translational research

DOI: https://doi.org/10.1177/26330040231219272

Front Neurol. 2023 ;14 1298569

The clinical spectrum of MELAS and associated disorders across ages: a retrospective cohort study.

Benjamin C Cox, Jennifer Y Pearson, Jay Mandrekar, Ralitza H Gavrilova.

Objective: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a severe multisystemic disease, although some have a milder phenotype. We aimed to evaluate the clinical spectrum of this disease from MELAS patients to asymptomatic carriers and identify predictors of severity.Methods: We reviewed 81 patients, who had MELAS or had positive genetics without meeting clinical criteria. Patients who met criteria including lactic acidosis, encephalomyopathy, and stroke-like episodes (SLE) were categorized as MELAS, symptomatic non-MELAS, and asymptomatic. MELAS was further categorized as "standard-onset" if the first stroke-like episode (SLE) occurred before age 40 or "late-onset."
Results: Eighty-one patients were included: 42 MELAS (13 late-onset), 30 symptomatic non-MELAS, and 9 asymptomatic. MELAS patients had lower BMI at onset (mean 18.6 vs. 25.1 asymptomatic and 22.0 symptomatic non-MELAS, p < 0.05). There was a trend toward higher serum heteroplasmy in MELAS compared to symptomatic non-MELAS and asymptomatic (means 39.3, 29.3, and 21.8% p = 0.09). Symptomatic non-MELAS had more sensorineural hearing loss as first presenting symptom (51.6% vs. 24.4%, p < 0.05). MELAS had higher prevalence of seizures (88.1% vs. 16.7%, p < 0.05) and shorter survival from onset to death (50% mortality at 25 years vs. 10%, p < 0.05). Late-onset MELAS had longer disease duration from first symptom to first SLE (mean 16.6 vs. 9.3 yrs) and also lived longer (mean age at death 62 vs. 30). Standard-onset MELAS had more neurologic involvement at onset than late-onset (51.7% vs. 15.4%). Late-onset patients had more prevalent diabetes (69.2% vs. 13.8%) and nephropathy (53.8% vs. 10.3%). Patients with late-onset MELAS also had more organ systems involved (mean 4.1 vs. 2.7, p < 0.05). There was a trend toward higher heteroplasmy levels in standard-onset (mean 44.8% vs. 25.3%, p = 0.18).
Discussion: Our study highlights the spectrum of MELAS. The lower BMI in MELAS at presentation as well as higher rates of sensorineural hearing loss as initial symptom in symptomatic non-MELAS may be useful clinical markers. While many patients present before age 40 with SLE, some can present with SLE later in life. Standard onset MELAS is more likely to present with neurologic symptoms. Late-onset is more likely to suffer diabetes or nephropathy and have more organ systems involved.

Keywords: MELAS; epilepsy; genetics; mitochondrial disease; myopathy; stroke

DOI: https://doi.org/10.3389/fneur.2023.1298569

Turk J Biol. 2023 ;47(5): 301-312

Mitochondrial transplantation and transfer: The promising method for diseases.

Gökhan Burçin Kubat.

Mitochondria are organelles that serve as the powerhouses for cellular bioenergetics in eukaryotic cells. It is responsible for mitochondrial adenosine triphosphate (ATP) generation, cell signaling and activity, calcium balance, cell survival, proliferation, apoptosis, and autophagy. Mitochondrial transplantation is a promising disease therapy that involves the recovery of mitochondrial dysfunction using isolated functioning mitochondria. The objective of the present article is to provide current knowledge on natural mitochondrial transfer processes, in vitro and in vivo applications of mitochondrial transplantation, clinical trials, and challenges associated with mitochondrial transplantation.

Keywords: Mitochondria; mitochondrial transfer; mitochondrial transplantation

DOI: https://doi.org/10.55730/1300-0152.2665