PKAN drug screening at Yale University

Since July 2021, a new one-year PKAN research project has been underway at Yale University, New Haven (USA) under the direction of Professor Choukri Ben Mamoun. The project entitled: "A High-Throughput Screening for PKAN-Revising Agents" is funded by a joint grant of $115,000 from Hoffnungsbaum e.V., Aisnaf and NBIA Disorders Association. We are contributing $47,500 (€40,595), also thanks to successful fundraising campaigns by some PKAN-affected families and numerous individual donations in favor of PKAN research.

PKAN (pantothenate kinase-associated neurodegeneration), one of the most common forms of NBIA, predominantly affects children, adolescents and young adults and is caused by two mutations in the PANK2 gene. These mutations lead to a deficiency of the PANK2 enzyme in cell metabolism and thus to PKAN disease. The main symptom of the disease is muscle spasms (dystonia), which sooner or later lead to severe disabilities. To date, there is no single approved therapy for PKAN that addresses the causes of the disease, but mainly symptomatic treatments. However, these can only inadequately mitigate the consequences of the disease.

Dr. Ben Mamoun, who is still relatively new to the field of PKAN research, is also in charge of another PKAN project, which we have already reported on:
https://www.hoffnungsbaum.de/forscher-an-der-yale-universitaet-arbeitet-an-neuem-therapieansatz-fuer-pkan/

Mamoun sees the limited knowledge of the metabolic and cellular defects caused by PANK2 deficiency as an obstacle to finding an ideal therapeutic strategy for PKAN and explains the project now jointly funded by NBIA Patient Support: "We hypothesize that an unbiased approach to discovering small molecules that restore normal function in PanK2-deficient cells may provide a better therapeutic strategy. The aim of our research is to use a cell-based detection approach to search for small molecules that restore normal metabolic function in cells from PKAN patients with Pank2 deficiency. The identified potential drug candidates will then be tested for their mode of action and biological activity in PKAN mouse models. The success of these studies will set the stage for future clinical testing of lead compounds for the treatment of PKAN.

We hope that this project, along with several other ongoing and upcoming PKAN research projects, can pave the way for new effective PKAN therapies. In the interests of those affected by PKAN, we believe that parallel research into various treatment options would be useful in the search for therapeutic solutions.