Target ALS and Alzheimer’s Drug Discovery Foundation announce award recipients for biomarker research

NEW YORK — Aug. 30, 2022 — Target ALS and the Alzheimer’s Drug Discovery Foundation (ADDF) announced today the first four award recipients in a new initiative to identify and develop biomarkers for neurodegenerative diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). A request for proposals was issued in January.

The partnership includes financial support from the ADDF’s Diagnostics Accelerator, a global research effort initiated by ADDF co-founder Leonard A. Lauder and Bill Gates with support from other leading philanthropists to fast-track the development of biomarkers and diagnostic tools for Alzheimer’s and related neurodegenerative diseases.

Discovery and validation of biomarkers will help researchers diagnose these diseases earlier, track their progression reliably and efficiently assess the effects of new drugs, leading to more efficient clinical trials.

Four projects were selected based on their potential to advance biomarkers for ALS and Alzheimer’s disease, FTD and other dementias. A brief overview of each newly funded project is provided below.

The members of the selected consortia receiving funding are as follows:

• Johannes Tröger (ki:elements), Jessica Robin (Winterlight Labs), Anja Schneider and Andreas Hermann (German Center for Neurodegenerative Diseases).
• Claudia Duran-Aniotz (Universidad Adolfo Ibañez), Alejandro Bisquertt Zavala (Neurognos), José   Manuel Matamala (Universidad de Chile), Agustin Ibañez and Andrea Slachevsky (Universidad Adolfo Ibañez) and Rolando de la Cruz (Universidad de Chile).
• Pietro Fratta (University College, London), Michael Ward (NIH/NINDS), Leonard Petrucelli and Mercedes Prudencio (Mayo Clinic).
• Magdalini Polymenidou (University of Zurich), Gianluigi Zanusso (University of Verona) and  Giuseppe Legname (Trieste International School for Advanced Studies).

Research has shown that neurodegenerative diseases like Alzheimer’s, ALS and FTD are heterogeneous in nature at the clinical, neuropathological and genetic levels, but they also share common features. Project funding established through this partnership will advance the long-standing search for biomarkers in each of these diseases and provide insights into their heterogeneity.

“These overlaps in the biology and genetics of diseases like ALS, Alzheimer’s and FTD offer promising new collaborative opportunities for disease-focused research that can have far-reaching impacts,” said Target ALS CEO Manish Raisinghani, M.B.B.S., Ph.D. “The work of these cross-sectoral and cross-disciplinary collaborative consortia has the potential to discover biomarkers to benefit ALS and other neurodegenerative disorders.”

“Partnerships like the one between the ADDF and Target ALS are essential in expanding our scientific knowledge of all neurodegenerative diseases so we can deliver effective treatments for patients and families with ALS, Alzheimer’s and other related dementias,” said Howard Fillit, M.D., co-founder and chief science officer at the ADDF. “We are committed to investing in and developing novel biomarkers that will provide us with simple, accessible and accurate ways to diagnose patients earlier than ever before and pave the way for new and innovative therapies.”

“There is much to discover about commonalities between ALS, FTD, Alzheimer’s and related dementias and a great value in looking at these diseases together,” said Niranjan Bose, managing director of health and life sciences at Gates Ventures. “This is an area that is still emerging and can benefit from philanthropic collaborations like the one between the Diagnostics Accelerator and Target ALS. Through this partnership, we hope to advance our understanding and make progress in identification of easily accessible biomarkers for better diagnosis and monitoring of these neurodegenerative diseases.”

Details of the Grantees:

PROSA — A low-burden, high-frequency prognostic digital speech biomarker to improve future confirmatory ALS and FTD trials

Johannes Tröger (ki:elements), Jessica Robin (Winterlight Labs), Anja Schneider and Andreas Hermann (German Center for Neurodegenerative Diseases)

This research is designed to develop and validate a biomarker based on short, high-frequency speech assessments that can be collected remotely. Changes in speech can be used to assess motor characteristics and cognitive abilities, including respiration, language, speech, executive function and memory. This research will improve understanding of similar patterns within patient groups to create a “yardstick” to measure changes that can be used to predict patient trajectory. The goals of the study are to improve patient characterization in ALS using speech assessments, validate and compare speech biomarkers to gold-standard clinical measures and develop a prognostic biomarker based on clinical outcomes at six-month follow-up.

Machine learning for the diagnosis and multimodal profile of neurodegenerative diseases based on circulating miRNA in Latin American population

Claudia Duran-Aniotz (Universidad Adolfo Ibañez), Alejandro Bisquertt Zavala (Neurognos), José Manuel Matamala (Universidad de Chile), Agustin Ibañez and Andrea Slachevsky (Universidad Adolfo Ibañez) and Rolando de la Cruz (Universidad de Chile)

The team is studying levels of micro RNAs (miRNAs) in blood plasma, which can be dramatically affected by the physiological and pathological changes associated with Alzheimer’s, FTD and ALS. This will be the first study to investigate miRNA biomarkers in Alzheimer’s, FTD and ALS from a Latin American and Caribbean cohort, establishing the feasibility required to expand the study to a larger number of participants and more countries across the region. Using data collected from 230 participants, the team hopes to develop a low-cost, noninvasive blood test for the detection of and differentiation between patients with these diseases.

Novel biomarkers to detect and monitor TDP-43 pathology in the ALS/FTD

Pietro Fratta (University College London), Michael Ward (NIH/NINDS), Leonard Petrucelli and Mercedes Prudencio (Mayo Clinic)

TDP-43 is a protein that normally lives in the nucleus of nerve cells, where it quality controls the processing of RNA. In ALS, TDP-43 is absent in nuclei, instead forming clumps in the periphery of cells. Researchers are currently unable to detect these abnormalities in living patients, which severely hinders the development of effective treatments.

To address this problem, the team decided not to focus on TDP-43 directly but on the by-products of its mis-localization. When TDP-43 is lost from the nucleus, highly specific mistakes in RNA and proteins occur. The team is developing and validating three types of tests that can detect these RNAs and proteins in the blood and the cerebrospinal fluid of patients to gain information about changes in TDP-43.

A biomarker for TDP-43 mis-localization would allow researchers to understand when the disease process starts in patients, aiding diagnosis and the start of potential treatments. It would allow them to assess the level of disease activity, showing whether patients are responding to specific treatments in clinical trials. It would also be essential in some other forms of dementia, such as frontotemporal dementia, where TDP-43 mis-localization occurs only in a subset of patients and cannot be identified with current tools.

Ultrasensitive detection of TDP-43 pathology with RT-QuIC of nasal swabs

Magdalini Polymenidou (University of Zurich), Gianluigi Zanusso (University of Verona) and Giuseppe Legname (Trieste International School for Advanced Studies)

The team aims to develop a test for the early detection of changes in TDP-43 pathology, which is implicated in certain forms of ALS and FTD, using a sampling procedure similar to the nasal swabs that were so broadly utilized during the COVID-19 pandemic. To achieve this, they will use a novel technique to detect pathological proteins called real-time quaking-induced conversion, or RT-QuIC, which can detect just traces of pathological TDP-43 in the cerebrospinal fluid of ALS and FTD patients. If successful, this test may be useful in healthy individuals in the future to perform large screening campaigns for TDP-43 pathology detection in presymptomatic stages of the diseases.