CoA Therapeutics launches phase 1 PKAN drug study

CoA logoJune 2021

CoA Therapeutics Inc., in April began a phase 1 study of the safety of a potential drug for Pantothenate Kinase-Associated Neurodegeneration (PKAN) by testing it in healthy volunteers.

The CoA Therapeutics team plans to begin clinical trials in PKAN patients in late 2022, once it is determined that the drug candidate they are calling BBP-671 is safe and a suitable dose for PKAN patients has been determined.

PKAN is one of the most common NBIA disorders.

The necessary preclinical animal studies with BBP-671 have been completed, and the Food and Drug Administration has approved the company’s application for the use of the Investigational New Drug in humans. Orphan drug designation has also been granted in both the US and Europe.

The patented compound changes the action of pantothenate, a key enzyme involved in metabolism, as it’s converted into CoA. CoA is deficient in PKAN individuals. The drug is a unique synthetic molecule that can immediately relieve  the movement disorder and extend the life span in a mouse model with brain CoA deficiency. It compensates for the missing CoA, and the company hopes it will have a similar affect in PKAN individuals.


Fundraising race is on for Million Dollar Bike Ride

MDBR logoApril 2021

June 12 marks the eighth annual Million Dollar Bike Ride and the second year it will be virtual because of the COVID-19 pandemic. If Team NBIA Disorders raises at least $20,000, every dollar will be matched, up to $30,000, to support a grant for BPAN research.

This is the fifth year Team NBIA is raising money to support new discoveries in BPAN, and anyone can take part — with as much or as little exertion as desired. Last year’s ride resulted in a $71,471 BPAN grant award.

The ride is organized by the University of Pennsylvania’s Penn Medicine Orphan Disease Center, and participants can cycle in their own neighborhood or even their living room. Others can support the team by spreading the word. Registration for riders is available at https://www.milliondollarbikeride.org/registration.

Choose Neurodegeneration with Brain Iron Accumulation when registering to be connected to Team NBIA Disorders. 

With the fundraising period heating up, anyone wanting to take part can register for $25 to join Team NBIA Disorders to cycle and raise donations by creating your own MDBR page with a link to send to friends and family to donate to your page. Those who don’t wish to create a fundraising page can register for $45, with the money going to Team NBIA Disorders as a donation toward the fundraising goal and then can participate in all the weekly challenges and cycling events.

Weekly challenges and classes for riders are in the works now. A virtual presentation is planned, along with a live spin class on June 12 at 11 a.m. EDT with pro  cyclist Nikki Theimann. As an added incentive, cyclists will be receiving goody bags this year.

Individuals who want to help but don’t want to register to ride can post  information about donating on social media or by sending an email to friends and family requesting their support for Team NBIA Disorders page at http://givingpages.upenn.edu/CureNBIA. Our team has made the match the last four years we’ve participated, and with your help, we will succeed again this year.

For more information, pictures and a video on Team NBIA Disorders and the  Million Dollar Bike Ride see https://www.nbiadisorders.org/mdbr-2021.



BPAN research moves ahead with grant from 2020 bike ride

BPAN researchersLeft to right: Drs. Lara Barazzuol, Mario Mauthe, Muriel Mari and Fulvio Reggiori
from University Medical Center Groningen in The Netherlands.

April 2021

A BPAN research grant that could inspire new approaches to treating the disorder was awarded in January through the University of Pennsylvania with collaboration from the NBIA Disorders Association.

The grant went to Drs. Fulvio Reggiori, Mario Mauthe, Muriel Mari and Lara Barazzuol from University Medical Center Groningen (UMCG) in The Netherlands. Their research project is titled “Deciphering the causes of mitochondrial network disruption in WDR45-defective cells and their contribution to the BPAN pathology.” It is designed to determine how gene mutations contribute to Beta-propeller Protein-Associated Neurodegeneration (BPAN), the most prevalent of the NBIA disorders.

Funds for the one-year grant were raised through the virtual Million Dollar Bike Ride (MDBR) fundraiser held in June 2020. Families raised $35,000 and $30,000 of that was matched, dollar for dollar, by Penn’s Orphan Disease Center. When combined with registration costs and additional sponsor funds, the research grant totaled $71,471.

This is the fourth time research supported by the NBIA Disorders Association qualified for Million Dollar Bike Ride grants. Our organization writes the request for proposals, and members of our Scientific & Medical Advisory Board review grant applications. The University of Pennsylvania manages the grants and sends us a copy of the final scientific report grant that recipients will provide. Selection is based on the grant proposal’s relevance, feasibility and scientific merit.

The WDR45 gene, which when mutated causes BPAN, produces a protein called WDR45 that appears to be involved in autophagy, the process in which the body’s cells clean out damaged or unnecessary components. However, the precise molecular function and contribution of this protein to this pathway remains unclear.

This research will be taking a closer look at the mitochondria, which are the small structures in cells responsible for important processes such as producing energy, regulating metabolism, inflammation and cell death. Mitochondrial dysfunction is observed in genes mutated in certain NBIA subtypes, including the PANK2 gene in PKAN, the COASY gene in CoPAN, the PLA2G6 gene in PLAN and the C19orf12 gene in MPAN, carry instructions for mitochondrial proteins.

The team’s preliminary data reveals that cells with a WDR45 deficiency have a disorganized mitochondrial network. This indicates that WDR45 is also part of other cellular processes in addition to autophagy. The main goal of the research is to characterize how WDR45 deficiency leads to mitochondrial network disorganization and unveil the consequences of this to the cell.

The research will initially be performed in model cell lines followed by experiments using stem cells, a type called induced pluripotent stem cells (iPSCs). These iPSCs come from donated BPAN patient urine cells that are reprogrammed to become iPSCs. The IPSCs can then be reprogrammed in a lot of other human cell body cells, including the key brain cells affected by BPAN.

The team will search for metabolic pathways, which are a series of connected chemical reactions in the cell, that are affected in BPAN patients due to their dysfunctional mitochondria. This knowledge could offer the possibility of developing treatments to rebalance these metabolic alterations and decrease the devastating symptoms of BPAN and, potentially, other NBIA disorders.

The project will take advantage of the expertise of the four researchers, who are strategically located at the same department of the UMCG: autophagy (Fulvio Reggiori), ß-propeller proteins (Mario Mauthe), brain organoids technology (Lara Barazzuol) and electron microscopy approaches (Muriel Mari).

This project is also benefitting from an ongoing collaboration between the awarded groups, Prof. Marina de Tijssen, a clinician at the Movement Disorders Groningen, which is the Netherlands center of expertise for NBIA diseases, and the Dutch NBIA foundation Stichting Ijzersterk.  Tijssen and the patient organization have been instrumental in getting in touch with the patient families donating the urine samples to generate the iPSCs.


NBIA Poland funds study to better understand MPAN’s causes

NBIA PolskaApril 2021

The association that represents all NBIA disorders in Poland has awarded a research grant for €59,000 ($71,571 U.S. dollars) to two researchers in a German Research Center who are investigating still-unanswered questions about the underlying causes of MPAN.

MPAN, which stands for mitochondrial membrane protein-associated neurodegeneration is caused by mutations of the C19orf12 gene.


Dr. Arcangela Iuso, researcher
from Helmholtz Zentrum Munich.

The grant to Dr. Arcangela Iuso and Dr. Ana Messias from the Helmholtz Zentrum Munich is to help fund a two-year research project on MPAN that started in September 2020. Titled “Investigating C19orf12 functions in redox metabolism,” the goal is to better understand how the mutation affects individuals and what drugs might help MPAN patients.


Dr. Ana Messias, researcher
from Helmholtz Zentrum Munich.

Preliminary studies have shown that when the gene C19orf12 is mutated, many processes in the cells are altered leading to MPAN, a progressive degenerative disease. In particular, cells from MPAN patients seem to have increased calcium compared to cells from healthy donors, and are more susceptible to oxidative stress, which occurs when the body has an excess of free radicals. This imbalance can lead to cell and tissue damage, which is part of what the researchers will study.

They also will use several molecular biology and biochemical methods to compare skin cells of MPAN patients to the cells of unaffected MPAN carriers (parents) and other healthy individuals. They want to see if there are significant differences between the cells of each group.
The researchers also will examine the proteins that are produced from the C19orf12 gene mutations. They will compare the normal protein found in healthy individuals to the mutated version that is found in individuals with MPAN.

The goal of comparing the healthy and MPAN cells and non-mutated proteins to the mutated ones is to find some differences that could be used to develop a therapeutic approach for MPAN. The researchers will then test different drugs that could reverse the cell damage in MPAN individuals. The team’s ultimate goal is to identify successful MPAN therapies.
Iuso and Messias will be collaborating and exchanging information with Drs. Marta Skowronska and Tomasz Kmiec, clinicians who see MPAN patients in Poland. Poland has the largest cohort of MPAN patients in the world, with over 45 individuals diagnosed to date.

NBIA Poland will support this project by facilitating scientific exchange between the Munich researchers and the Polish researchers and by making the MPAN patient community aware of the importance of donating biosamples for the research project.

Anyone interested in donating a biosample to the research group should contact Dr. Maciej Cwyl, President of NBIA Poland at mc@il.pw.edu.pl.



Scientific & Medical Advisory Board welcomes two new members

April 2021

Two new members recently joined the NBIA Disorders Association’s advisory group of expert researchers and physicians, while two others say farewell.


Professor Robin Ketteler
of University College London, UK.

The newest members of the association’s Scientific & Medical Advisory Board (SMAB) are Professor Robin Ketteler, a researcher-manager of the High-Content Screening Core Facility at the Laboratory for Molecular Cell Biology, University College London, and Dr. Valeria Tiranti, head of the Molecular Pathology of Mitochondrial Disorders lab at the IRCCS Foundation Neurological Institute Carlo Besta in Milan, Italy.

Ketteler has been recognized as a leader in high-content biology and CRISPR genome editing, specializing in the early steps in autophagy, the natural process in which the body's cells clean out any damaged or unnecessary cells. The Ketteler lab is developing therapeutic approaches to target the autophagy pathway in cancer and neurodegenerative disorders. These include the use of patient-derived cells and the use of stem cells for disease modelling and drug screening.


Dr. Valeria Tiranti, of IRCCS
Foundation Neurological Institute
Carlo Besta in Milan, Italy.

Tiranti’s expertise is in mitochondrial and metabolic disorders, including identification of disease genes, molecular and cellular biology, and identifying the causes of disease. She joined the NBIA field some years ago and is studying the role of mitochondria in neurodegeneration by examining cellular and animal models.

Ketteler and Tiranti replace two dedicated, distinguished SMAB members, Dr. Arnold Strauss and Dr. Suzanne Jackowski, both of whom served as expert advisers from 2016 to 2020. Strauss and Jackowski have retired from their research institutions and stepped down from the board at the end of last year. Strauss was a researcher and professor of pediatrics in cardiology at Cincinnati Children’s Hospital and the University of Cincinnati, and Jackowski was a biomedical scientist and faculty member at St. Jude Children’s Research Hospital. The NBIA Disorders Association board will greatly miss their knowledge and expertise.

For more information about our Scientific & Medical Advisory Board, please see our website:

Scientific & Medical Advisory Board




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