This document discusses the history of Alstrom syndrome, a rare genetic disorder, and the journey to developing effective treatments. It describes: - Carl Alstrom's initial identification and description of the syndrome in 1946 based on his observations of three related patients. - Key characteristics of Alstrom syndrome including childhood obesity, insulin resistance, hearing loss, and multi-organ fibrosis. - The experiences of two patients, Matthew and Charlotte, who experienced multiple misdiagnoses before receiving a correct Alstrom syndrome diagnosis in their late teens. Both ultimately died due to heart and organ failure. - Milestones in establishing patient organizations and clinical networks in the late 1990s and 2000s that helped increase understanding and care for Al

1. The fight for treatments for
an Ultra Rare Disease. Case
study: Alstrom Syndrome
Re-imagining this patient
journey.
Kay Parkinson
CEO
Cambridge Rare Disease
Network
www.camraredisease.org

2. Carl Henry Alstrom -1946
Serafimerlasarettet Hospital 1946 - 14 year old
boy who appeared to have symptoms similar
to the Laurence-Moon-Bardet-Biedl
Syndrome, patient’s condition was different in
several important ways. The child had retinal
degeneration and obesity bearing a similarity
to LMBBS, but also exhibited neurological
hearing impairment and normal mental
development
Further investigation revealed that the young
man had two second cousins, a boy and a girl
about ten years older, with similar but more
pronounced features. Alström and his co-
authors, B. Hallgren, IB Nilsson and H
Asander described these three patients in an
elegant and very thorough manuscript
published in 1959, detailing the apparently
recessive hereditary combination of retinal
degeneration, obesity, sensorineural hearing
loss, and diabetes. The new syndrome was
known for a short time as the Alström-Hallgren
syndrome, but later was designated simply
Alström Syndrome.

3. Key Eligibility Criteria
Alström Syndrome : Overview
Alström Syndrome 1 (ALMS1), a rare autosomal recessive
disease (mutations in a large gene located on chromosome
2p13- identified in 2002). Alström Syndrome, is a fibrotic multi-
organ disease, with gradual unfolding of phenotypes.
Characterized by childhood onset obesity, extreme insulin
resistance, type 2 diabetes mellitus (T2DM), dyslipidaemia,
hypertension, and multi-organ fibrosis.
Other features include retinal cone-rod dystrophy, hearing loss,
short stature, cardiomyopathy progressive cardiac, pulmonary,
hepatic, and renal dysfunction.
Complex, varied clinical picture.
Leads to delays in diagnosis. Reduced life expectancy.
Clinical challenges to develop treatment strategies and need for
specialised multi-disciplinary clinics.
Subject recruitment is a major challenge for clinical trials.
Figure 1.
Frequency, mean
age at onset, and
age range of
selected clinical
features in Alström
Syndrome
Arch Intern Med. 2005;165:675-683

4. Matthew and Charlotte
They will have 4 mis-diagnosis and will not be
correctly diagnosed until aged 18 and 16.
Consequences-
Matthew will survive a week following a heart
transplant at age 25 –Charlotte will not survive
a heart/kidney transplant age 29
Autopsies show all organs are fibrotic.

5. 1998 Alström Syndrome UK
founded
1
Alström
Syndrome UK
charity is
founded and
the first family
conference is
held in 1998.
2
7 Families
attend.
3
1999 Doctors
hold impromptu
clinics in hotel
rooms
4
Doctors gain
understanding
through seeing
more patients.
Patients and
doctors work
together to
develop better
care .
5
We start up a
web site
www.alstrom.
org.uk and
begin to
develop family
support.
6
NHS
Specialised
Commissioning
obtained 2008
2013
EURORDIS
Patient
Organisation of
the Year

6. www.alstromeurope.org
• Join EU WABB- meet clinicians from across
the EU
• 2013 Alstrom Syndrome Europe founded- to
link medical professionals - increasing the
number of patients for clinical trials.
• Attended the World Orphan Drug
Conference in Geneva 2013–displayed a
poster on Alstrom Syndrome detailing the
fibrosis affecting multiple organs.
• A bank of skin fibroblasts had been
assembled as part of a Big Lottery Grant.
• Prometics requested access to these.
• Four years later the skin fibroblast have still
not been sent!

7. PROMETICS
Meeting
2013
Serendipity?
A new
treatment? –
Approached by
Pierre Laurin –CEO
of PROMETICS who
had a new drug that
treated fibrosis.
Doctors not
prepared to take the
risk to try the drug?
Wanted a mouse
model first.
Evidence mounts of
its effectiveness and
a trial begins with
UK adult patients in
January 2016.

8. Timeline – why so long?
Re-image this time line!
1949
Alstrom Syndrome
recognised as a
medical condition
1959
Paper published
on Alstrom
Syndrome
1978
Matthew born-
1978 diagnosed
1998
1981
Charlotte born
1981–diagnosed
1998
1998
Alstrom
Syndrome UK
charity founded
with 7 patients-
today over 70
patients
2013
Alstrom Europe
started with
partners in UK,
Italy, France,
Spain, Turkey,
Poland and
Sweden with over
250 patients.
2013
Prometics
meeting at World
Orphan Drug
Conference in
Geneva
2016
Trial begins in UK
and talks with the
rest of the EU