Awarded a one-year, $100,000 grant from Pachyonychia Congenita Project. Project Title: Keratin 16 provides a new paradigm for keratin function in palmoplantar skinPrincipal Investigator (PI) Name: Pierre A. Coulombe, PhDPI Affiliations: University of Michigan Medical School
Continue Reading Pierre Coulombe: 2025 PC Grant Award Recipient
Awarded a one-year, $19,950 grant from Pachyonychia Congenita Project. Pachyonychia congenita and palmoplantar disorders are rare, painful, and inherited skin and nail disorders. We intend to employ advanced genetic testing methods on several affected families from diverse Pakistani ethnicities with these disorders in order to find the specific faulty genes responsible for these conditions. We hope to discover new genes that have not been linked to these disorders before. The ultimate goal is to use these discoveries to improve diagnosis and develop better treatments for patients with these disorders. Project Title: Genetic Elucidation of Inherited Pachyonychia Congenita and Palmoplantar Disorders Segregating inInbred Families: Insights into Disease PathogenicityPrincipal Investigator (PI) Name: Sajid MalikPI Affiliations: Human Genetics Program, Department of Zoology, Quaid-i-Azam University, Islamabad Abstract Background: Pachyonychia Congenita (PC; OMIM 167200) and related Palmoplantar Disorders (PD; OMIM 144200) are rare, painful, and debilitating keratinization disorders characterized by nail dystrophy, palmoplantar keratoderma, leukokeratosis,…
Awarded a one-year, $100,000 grant from Pachyonychia Congenita Project. To thoroughly understand pachyonychia congenita, this disease ought to be studied in models. A mouse models was recently generated. It offers the opportunity to investigate pachyonychia congenita at the cell and molecular levels. Knowledge gained from this investigation is valuable for guiding the development of novel therapies. Project Title: Defining molecular mechanisms underlying hyperkeratosis of pachyonychia congenita in a mouse modelexpressing a mutant of Krt6aPrincipal Investigator (PI) Name: Jiang Chen, MDPI Affiliations: Department of Dermatology, Stony Brook University Abstract Genetically engineered mouse models capable of recapitulating diseases at genetic and phenotypic levels are valuable for the understanding of disease mechanisms. They can also be used as platforms for testing novel therapies. A mutation was recently introduced into the Krt6a gene. This mutation is homologous to a frequently reported mutation in pachyonychia congenita (PC) patients. Consistent with patients, heterozygous mutant mice exhibited…
Awarded a two-year, $145,447 grant from Pachyonychia Congenita Project. Pachyonychia congenita (PC) is a rare genetic skin condition that causes thick, painful skin on the hands and feet, making walking and daily activities difficult. This project aims to closely study PC skin at a very detailed level to understand which cells and biological pathways are not working properly and how this differs between patients. By identifying these problem pathways, we can match them to existing medicines that may reduce pain and skin thickening more effectively. The results will help move PC treatment toward more personalized, targeted therapies that can significantly improve patients’ quality of life. Project Title: Elucidation of key molecular pathways in Pachyonychia Congenita at spatial single-cell resolution to guide precision-targeted therapiesPrincipal Investigator (PI) Name: Alain Hovnanian, MD, PhDPI Affiliations: INSERM, Imagine Institute for Genetic Diseases, Necker Hospital for Sick Children, Paris University Abstract Pachyonychia Congenita (PC) is a…
Continue Reading Alain Hovnanian: 2025 PC Grant Award Recipient
Awarded a one-year, $100,000 grant from Pachyonychia Congenita Project. Of all of the features of Pachyonychia Congenita, pain in the hands and feet arguably has the most negative impact on quality of life, and is frustratingly difficult to treat. We propose to use genetically engineered mice that mimic PC or similar hereditary skin disorders to pinpoint the molecules that drive the exaggerated pain sensation. Armed with this information, the field will be able to identify new strategies to block those molecules and diminish pain in individuals with PC and possibly other related painful skin conditions. Project Title: Identifying Molecular Drivers of Pain in Hereditary Palmoplantar KeratodermasPrincipal Investigator (PI) Name: Michael J. Caterina, MD, PhDPI Affiliations: Dept Neurosurgery, Johns Hopkins University School of Medicine Abstract Pain is the most life-impacting feature of Pachyonychia Congenita and some other hereditary palmoplantar keratodermas. Unfortunately, pain in individuals with PC is often refractory to treatment.…
Continue Reading Michael Caterina: 2024 PC Grant Award Recipient
Awarded a one-year, $99,206 grant from Pachyonychia Congenita Project. All potential therapies for PC (Pachyonychia Congenita), from traditional drug molecules to advanced gene-editing approaches, must eventually confront a common challenge: delivery of the therapeutic agents into the upper layer (also known as epidermis) of skin covering the bottom of the foot (also known as plantar skin), which is the target treatment area for the most problematic symptom of PC – the development of excessive and often debilitatingly painful calluses. Ideally PC therapies would be delivered directly to these skin areas, to minimize side effects and other problems that often occur when drugs are circulated through the entire body. However the skin’s ability to protect us from the outside world also becomes a significant impediment against delivering drugs into the skin. There are existing technologies to overcome this barrier and enable drug delivery into the skin, but they have predominantly been…
Awarded a one-year, $50,000 grant from Pachyonychia Congenita Project. Pachyonychia congenita (PC) is one of several inherited skin diseases caused by mutations in keratin genes, which are responsible for forming a scaffold within skin cells that gives the skin strength. PC patients develop symptoms at the body locations where PC keratins are expressed, such as the skin on the palms and soles, at least in part because of localized skin fragility. We are trying to understand if the unique symptoms of PC result simply from the unique expression pattern of PC-keratins or if PC-causing mutations affect skin cells differently from mutations that cause other keratin-related diseases. To do this, we are building a skin organoid model that lets us directly compare different keratins and keratin mutations that are not expressed at the same body location, which may help us find new ways to treat the unique symptoms of PC. Project…
Continue Reading Benjamin Nanes: 2024 PC Grant Award Recipient
Awarded a one-year, $99,960 grant from Pachyonychia Congenita Project. Pachyonychia congenita (PC) is a genetic disease primarily characterized by abnormal nails as well as thickening of the skin of the palms, resulting in painful plantar skin that greatly impacts patients’ quality of life. There is no cure for PC and treatment is mainly supportive. The goal of this study is to investigate the factors that are abnormally expressed in the skin and blood of PC patients, with the aim of developing specific therapies that can normalize the expression of these factors and improve disease severity and patients’ quality of life. Project Title: Systematic mapping of druggable pachyonychia congenita-associated targetsPrincipal Investigator (PI) Name: Eli Sprecher, MD, PhDPI Affiliations: Division of Dermatology & Deputy Director General for R&D and Innovation, Tel-Aviv Medical Center, & Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Abstract Pachyonychia congenita…
Continue Reading Eli Sprecher: 2024 PC Grant Award Recipient
Awarded a total amount of €55,500 in installments of €18,500 per year for three (3) years. The funding will be awarded in collaboration with the EI Cure Project paying an equal amount of funds per year for the duration of the grant period of three (3) years. “Delivery of keratinocyte-targeting nanocarriers loaded with gene editing tools to skin” Summary: To explore methods of delivery with gene-editing for topical delivery to the skin. The primary objective is to explore methods to transfect base-editing tools through the skin barrier using a lipid nanoparticlecarrier. Proposed methods include direct topical application, use of lasers, and use of micro-needling to permeate the skin barrier. The primary target for gene-editing is the DNA of skin cells including stem cells located in the base layer of the epidermis. The secondary objective is to establish the efficacy of gene-editing needed to result in curative treatment of keratin-mutation related…
Continue Reading PC Project Awards Gene Editing Delivery Grant
Awarded a one-year, $88,200 grant from Pachyonychia Congenita Project. The main problem of patients with PC is the intense pain they feel when walking. This is due to the malfunction of some skin-forming proteins, especially in the soles of the feet. This malfunction is due to errors (mutations) in the instructions carried by the genes encoding these proteins. Our project is based on correcting these errors directly in the skin of the patients so that the proteins function correctly again and thus mitigate the pain that patients suffer when walking. To achieve this, we will design tools to cut at the DNA location of the genetic defect using a kind of molecular scissorscalled CRISPR. Once the erroneous DNA has been cut out, we will be able to remove the disease-causing DNA copy to recover the precise instructions needed for the proteins to function normally again. We will test various methods…
Continue Reading Marta Garcia Diez: 2023 PC Grant Award Recipient
Awarded a one-year, $97,500 grant from Pachyonychia Congenita Project. Pachyonychia congenita (PC) is characterized by excessive callus formation which is caused by thickening of the outer layer of the skin, the epidermis. To form the epidermis, the resident cells have to undergo drastic changes to lose a major fraction of their content with the help of the cellular garbage bins, the lysosomes. We could previously show that lysosomes do not work properly in PC. We therefore want to explore if modulation of lysosomes helps to ameliorate callus formation in PC. Project Title: Lysosomes in the pathogenesis of pachyonychia congenitaPrincipal Investigator (PI) Name: Nicole Schwarz, PhDPI Affiliations: Institute of Molecular and Cellular Anatomy, RWTH Aachen University AbstractPachyonychia congenita (PC) is a hereditary skin disease that is caused by mutations in keratin genes 6, 16 and 17 and is characterized by painful palmoplantar keratoderma. We have previously shown that, in PC patient-derived…
Continue Reading Nicole Schwarz: 2023 PC Grant Award Recipient
Awarded a one-year, $100,000 grant from Pachyonychia Congenita Project. The project aims at improving the understanding of the disease mechanisms involved in painful plantar keratoderma in PC patients. It will compare the expression of genes and proteins involved at a global and cellular level. This study will allow to identify the different cell types and biological pathways responsible for abnormal keratinization and pain. This work has the potential to uncover new therapeutic targets and will guide repurposing of existing drugs for PC patients. Project Title: Integrative mRNA sequencing, proteomics and phosphoproteomics in pachyonychia congenitaPrincipal Investigator (PI) Name: Alain Hovnanian, MD, PhDPI Affiliations: Inserm UMR1163 Abstract PC is a rare genodermatosis characterized by very painful palmoplantar keratoderma, oral leukokeratosis, nail dystrophy and cysts. It is caused by dominant mutations in keratin genes KRT6A, KRT6B, KRT6C, KRT16, and KRT17. The understanding of PC pathophysiology is incomplete despite recent progress. There is no…
Continue Reading Alain Hovnanian: 2023 PC Grant Award Recipient
Awarded a two-year, £144,581 grant from Pachyonychia Congenita Project. Several genetic skin conditions specifically affect the skin found on our palms and soles (palmoplantar), including the palmoplantar keratodermas (PPKs). PPKs are characterised by a thickening of palmoplantar skin, which is often accompanied by pain when walking, as in pachyonychia congenita. The skin forms a vital barrier between the human body and the environment and palmoplantar skin is uniquely adapted to provide this barrier function whilst withstanding high levels of mechanical stress. Compared to hairy skin covering the rest of the human body, it is thicker, hairless and has a distinctive gene expression pattern. Many of the genes mutated in inherited PPKs are only significantly expressed in palmoplantar skin, and yet this specialised skin is relatively understudied and the biological differences in palmoplantar skin are not well understood. Consequently, current PPK disease models grown in the lab based on skin cells…
Continue Reading Diana Blaydon: 2022-2023 PC Grant Award Recipient
