In the age of precision medicine, researchers who want to determine if a new drug is working to treat scleroderma, a rare autoimmune condition that results in hardening of the skin and internal organs, there are no high-tech genetic tests to evaluate their efficacy. Instead, there is a skin-pinch test.
Researchers blame this low-tech test, in part, for the routine failure of potential scleroderma drugs in clinical trials.
Modernizing the evaluation of potential drug therapies was the focus of the three-day Scleroderma Diagnosis Sandpit hosted by Scleroderma and Raynaud’s UK (SRUK) February 26-28 at the Wellcome Collection in London. Twenty-four researchers from disparate fields came together at the KI-facilitated event to form new teams, develop innovative approaches for treating scleroderma and made pitches for funding those research projects.
“Despite the progress we’ve made in the last 20 years, treatment for scleroderma remains inadequate,” says Christopher Denton, Ph.D., FRCP. Denton is Head of Centre and Consultant Rheumatologist, University College London, Division of Medicine. “We know from previous clinical trials that drugs used routinely for skin and lung fibrosis are helpful to some extent, but do not help all cases and the benefits are limited.”
The name scleroderma comes from the Greek “sclero” or hard and “derma” or skin. It affects 19,000 in the U.K. and 2.5 million worldwide. The disease results in abnormal production of collagen, or fibrosis, which causes thickening of the skin and, in advanced cases, internal organs.
Denton says the current assessment tools, including the skin score, are limited by subjectivity and the time needed to train people. “We need to make sure that new treatments are evaluated in the best and most robust way so that we can make more progress and discontinue approaches that do not work.”
Denton served as an evaluator of the proposals generated by the teams that formed at the Sandpit. “The teams came up with new approaches that tackle important unmet medical needs,” he says.
Including Patients
A key strategy of the Sandpit was the inclusion of patients in the Sandpit in order to come up with patient-focused solutions. Georgina Pantano, a 34-year-old patient diagnosed with scleroderma in 2012, served as a mentor at the Sandpit. At the time of her diagnosis, Georgina had never even heard the word scleroderma, nor had she heard of a similar condition called Raynaud’s. The Buckinghamshire resident first went to her general practitioner with typical Raynaud’s symptoms: fingers that would turn blue with even the slightest temperature change.
“Then I started getting swelling in my fingers, pain and stiffness in my wrists and forearms. Being a beauty therapist, it was put down to repetitive strain at the time,” Georgina recalls.
Over the course of 18 months, Georgina’s symptoms progressed to debilitating joint pain, shortness of breath and fatigue. Doctors could not explain her symptoms. Ultimately, when she got a second opinion and an accurate diagnosis, Georgina required immediate treatment upon diagnosis. That’s because her lungs and oesophagus were hardening, which could have been life-threatening.
Georgina says living with scleroderma, for her, means adjusting to a ‘new normal,’ one characterized by pain, fatigue and time-consuming mainstream and alternative treatments to reduce pain and preserve mobility.
Georgina says she feels that having patients take part in the Sandpit was hugely beneficial. “Being a rare disease, some people were not as familiar with the condition. Being able to help educate them felt extremely important and invaluable.” She also says hearing the proposals made her feel optimistic about their potential to help patients like herself.
Diagnostic Path Forward
Established in April 2016, SRUK sought input from patients, physicians and other stakeholders to fully understand the challenges they faced. These challenges included lack of awareness, poor time to diagnosis and lack of effective treatments.
“In rare disease research, we know that real progress can only be achieved when we work together,” says Sue Farrington, Chief Executive of SRUK. “But what the Sandpit demonstrated to me is how that progress can be truly accelerated by bringing people together from totally different disciplines.”
Farrington also says she was impressed by the quality of the output generated in three days. “It was also inspiring to witness the connections being made as people from completely different disciplines spotted opportunities to add value to one another’s work. We are optimistic that the work generated will lead to some novel solutions for tackling the diagnostic pathway for Scleroderma.”