Towards a therapy for patients with Osteogenesis Imperfecta (OI)
(van Dijk F, UMC Groningen, Isala Expertise Center/The Netherlands
Dr. Fleur van Dijk will combine gene therapy with cell therapy by creating induced pluripotent stem cells (iPSC) from patient derived cells. iPSC are derived from skin or blood cells that have been reprogrammed back into an embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes. The researcher will then correct the disease-causing mutation with CRISPR-Cas9 technology and differentiate the corrected iPSC towards bone forming cells. Next, this procedure will be performed in OI mice and corrected osteoblasts will be transplanted in OI murine models for safety and efficacy studies. If this approach is successful, a clinical phase I trial will be prepared.
RESEARCH BRIEF available here.
Vitamin K status in children with O.I.
(Zoer B, Medical Biologist VU (Vrije Universiteit) Amsterdam / van Dijk A.T.H, Paediatrician, Wilhelmina Children’s hospital)
The goal of this research is to assess whether vitamin K levels in children with O.I. are lower than in healthy children. Given that Vitamin K is required in the normal bone metabolism and the bone metabolism of children with OI is higher than normal, more Vitamin K may be needed for optimal bone formation. If this proves to be true, the next step will be starting vitamin K supplementation therapy in a clinical trial. This is a potential very easy treatment option to achieve better bone health and growth in children with O.I. Whilst it would not eliminate OI, it would lead to improvements with no known side effects.
Eat, breathe, sleep with OI.
(Lo Mauro A, Politecnico di Milano Dipartimento di Elettronica)
The improvement of body composition by adequate nutritional and controlled dietary intake may have long-lasting ameliorative effects on the quality of life in OI by: 1) decreasing body weight; 2) supplying the adequate energy; 3) reducing the incidence of nocturnal obstructive apnoea’s; 4) reducing the burden on the thorax while breathing and 5) improving physical activity and mobility, particularly during wheelchair transfer.
To test this hypothesis, the researcher will involve 30 people with a severe form of OI into a multidisciplinary study. They will verify the impact of six months of controlled dietary regime (Italian patients) on the quality of breathing, sleeping and living with respect to six months without nutritional intervention (British patients). The results of this project are expected to be available by end 2020.
Targeting Gene Repair to Bones
(Munns C and Schindeler A, The Centre for Children’s Bone and Musculoskeletal Health Australia)
A major challenge with using gene therapy to treat bone fragility disorders is the difficulty associated with delivering reparative DNA to bone cells. Embedded within the skeleton, bone cells can be difficult to access and often take up DNA poorly. Thus even with the development of new technologies such as CRISPR that can successful edit genes in a targeted way, gene therapy will not be possible unless such vectors can be targeted to the bone cells.
The research goal is to develop a highly efficient system for the delivery of DNA vectors to bone cells, adeno-associated viruses (AAVs) The research goal is to develop a high-efficiency system for the delivery of DNA vectors to bone cells. Adeno-associated viruses (AAVs) are a group of naturally occurring viruses that have been isolated and engineered for use in the lab and also clinically. Clinical trials using AAV to treat various genetic conditions have already been undertaken, although not yet in the context of bone. AAV are favoured as a viral method of gene therapy as they do not generate a high immune response nor do they integrate into the genome.
The researchers of this proposal have agreed to exchange knowledge with Dr. Fleur van Dijk, seeking to enhance each other’s research impact.
Assessment of Bone Quality in OI Zebra fish Models.
(Willaert A, Ghent University)
Animal models are an indispensable part of research before it is applied on humans. Most frequently, research is performed on mice, in particular the “Brtl mouse” model, a mouse with OI.
In the last couple of years a new animal model has gained popularity: The OI-zebra fish. It is expected to be a much more cost effective and faster way to test new medication compared to the methods currently available. The researcher, associated with the university of Gent is a pioneer in the field of zebra fish research and Care4Brittlebones has decided to support his important work with a small grant to recognize his achievements in this area.
Psychosocial impact of Osteogenesis Imperfecta
(Foundation Care4BrittleBones in collaboration with van Wijk I (UMC Utrecht), Harsevoort A (Isala Zwolle) and Zoer B (VOI))
OI is a purely physical disorder. Research and treatment have therefore focussed on these aspects. However people with OI and most professionals working with OI are recognizing that OI can also have a significant psychosocial impact. This may look differently in various stages of life and the nature of the impact depends also on the severity of OI and the individual person.
Care4BrittleBones is taking the lead in this project, which is partnering with the two Dutch national Expertise Centers and the patients’ association (VOI). The project has undertaken a survey, held focus groups and interviews to inventorise the psychosocial issues experience by people with OI – children, adolescents, adults and people with OI older than 50 years. More than 200 people with OI of all ages have participated. Based on the outcome of this work, various tools and processes will be developed in 2019. The project is focusing on the Netherlands, as it has been enabled by a grant from the Dutch Zorginstituut Nederland. The results of the work will be translated into English to make it available internationally.
The ambition of the four cooperating organizations is that by 2020 every child (or parents), youth, adult and elderly with OI in the Netherlands is aware that different psychosocial consequences can occur in OI, and has access to appropriate care.
The results of this project are expected to be available by end 2019.