Monday, January 17, 2022

Adalia Rose Williams and progeria

 Adalia Rose Williams, a 15-year-old YouTuber who was born with a rare genetic disorder called progeria, has died, her family have confirmed. 

In a statement posted to Facebook and Instagram, the family said Rose passed away in the evening of January 12, 2022, and that she had finally been "set free from this world." 

Rose had amassed nearly three million subscribers on her YouTube channel, with which she documented her life and struggles with her condition. 

The family, which had recently moved to San Antonio, Texas, from Austin, said in the statement: "She came into it quietly and left quietly, but her life was far from it. She touched MILLIONS of people and left the biggest imprint in everyone that knew her. She is no longer in pain and is now dancing away to all the music she loves. I really wish this wasn't our reality but unfortunately, it is." 

"We want to say thank you to everyone that loved and supported her. Thank you to all her doctors and nurses that worked for YEARS to keep her healthy. The family would now like to mourn this huge loss in private." 

What Is Progeria? 

Progeria, also known as Hutchinson-Gilford Progeria Syndrome, or HGPS for short, is a very rare genetic disease that essentially causes children to age rapidly. 

Children with the condition appear to be healthy at birth but usually begin to show signs of rapid biological aging within the first two years of their life. 

The condition is very rare, affecting only around one in 20 million people worldwide, according to the Cleveland Clinic. Progeria is equally common in boys as it is in girls. 

The disorder is caused by a mutation in a single gene known as lamin A (LMNA) that makes a protein necessary for holding the center—or nuclei—of cells together. 

When this gene is mutated, it produces an abnormal form of the LMNA protein called progerin, which makes cells unstable and results in the rapid aging seen in progeria. 

There are no known risk factors—environmental, lifestyle, or others—that may increase the risk of having progeria or giving birth to a child with the condition. Unlike many genetic disorders, progeria does not run through families. In fact, the chances of parents having a second child with the condition are around 2-3 percent, according to the Mayo Clinic. 

Signs and symptoms of the condition usually appear in the first year of life, as the child's growth slows significantly, while their motor development and intelligence remains normal. 

The main signs and symptoms of the progressive disorder include: slowed growth leading to below average height and weight; a narrowed face, with a small lower jaw, thin lips and beaked nose; a head that is disproportionately large compared to the face; prominent eyes and inability to completely close the eyelids; hair loss, including eyelashes and eyebrows; thinning, spotty and wrinkled skin; visible veins; and a high-pitched voice. 

The condition is usually accompanied by several health issues, including severe progressive heart and blood vessel disease; hardening and tightening of skin in some parts of the body; abnormal tooth formation; some hearing loss; loss of fat that lies beneath the skin as well as muscle mass; skeletal abnormalities and fragile bones; stiff joints; and hip dislocation. 

The average life expectancy of a child with progeria is around 13 years, according to the Mayo Clinic, although some individuals die younger while others live to around the age of 20. Complications related to cardiovascular issues represent the most common cause of death for people who have progeria. 

There is currently no cure for progeria, although the U.S. Food and Drug Administration approved the first ever treatment for the disease in 2020 that provides some improvement in one or several areas of the condition.



  1. A team at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) and the Spanish Cardiovascular Research Network (CIBERCV), both Spain, have created the first animal model to develop Hutchinson-Gilford Progeria Syndrome (HGPS). Using the new model, the researchers have demonstrated that it is possible to treat HGPS.

    HGPS is caused by a mutation in the LMNA gene and is characterised by accelerated ageing and death in the second decade of life, principally due to cardiovascular complications derived from atherosclerosis. In the absence of mutations, LMNA encodes type A lamin proteins (Lamins A and C). The mutation found in HGPS patients results in the synthesis of progerin, a mutant protein that provokes multiple molecular and cellular alterations in the tissues where it accumulates, causing their life to pass at an highly accelerated rate.

    Joint first authors Drs Amanda Sánchez López and Carla Espinós Estévez explained that while some palliative progeria therapies are effective in animal models, their therapeutic benefit is very limited. “A true cure would require the elimination of the culprit mutation,” commented López. However, this is not yet possible and progeria is only diagnosed once the first symptoms have already appeared. “We therefore sought to reverse symptoms once they are already present and to determine how long treatment could be delayed and still have a beneficial impact,” explained Estévez.

    The team used CRISPR-Cas9 technology to generate HGPSrev mice and found that elimination of progerin and restoration of lamin A expression increased life expectancy by 84.5 percent in HGPSrev mice with very mild symptoms. Moreover, this approach extended lifespan by 6.7 percent, including in mice with very advanced symptoms.

    These results establish not only that starting treatment when symptoms are mild has a huge positive impact, but also that treatment can be beneficial no matter how late it is started. The study, published in Circulation, also establishes that the cardiovascular alterations and early death associated with HGPS can be prevented with treatments specifically targeting cells of the cardiovascular system.

  2. Sánchez-López A, Espinós-Estévez C, González-Gómez C, Gonzalo P, Andrés-Manzano MJ, Fanjul V, Riquelme-Borja R, Hamczyk MR, Macías Á, Del Campo L, Camafeita E, Vázquez J, Barkaway A, Rolas L, Nourshargh S, Dorado B, Benedicto I, Andrés V. Cardiovascular Progerin Suppression and Lamin A Restoration Rescue Hutchinson-Gilford Progeria Syndrome. Circulation. 2021 Nov 30;144(22):1777-1794. doi: 10.1161/CIRCULATIONAHA.121.055313. Epub 2021 Oct 25. PMID: 34694158; PMCID: PMC8614561.

    Background: Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder characterized by premature aging and death mainly because of myocardial infarction, stroke, or heart failure. The disease is provoked by progerin, a variant of lamin A expressed in most differentiated cells. Patients look healthy at birth, and symptoms typically emerge in the first or second year of life. Assessing the reversibility of progerin-induced damage and the relative contribution of specific cell types is critical to determining the potential benefits of late treatment and to developing new therapies.

    Methods: We used CRISPR-Cas9 technology to generate LmnaHGPSrev/HGPSrev (HGPSrev) mice engineered to ubiquitously express progerin while lacking lamin A and allowing progerin suppression and lamin A restoration in a time- and cell type-specific manner on Cre recombinase activation. We characterized the phenotype of HGPSrev mice and crossed them with Cre transgenic lines to assess the effects of suppressing progerin and restoring lamin A ubiquitously at different disease stages as well as specifically in vascular smooth muscle cells and cardiomyocytes.

    Results: Like patients with HGPS, HGPSrev mice appear healthy at birth and progressively develop HGPS symptoms, including failure to thrive, lipodystrophy, vascular smooth muscle cell loss, vascular fibrosis, electrocardiographic anomalies, and precocious death (median lifespan of 15 months versus 26 months in wild-type controls, P<0.0001). Ubiquitous progerin suppression and lamin A restoration significantly extended lifespan when induced in 6-month-old mildly symptomatic mice and even in severely ill animals aged 13 months, although the benefit was much more pronounced on early intervention (84.5% lifespan extension in mildly symptomatic mice, P<0.0001, and 6.7% in severely ill mice, P<0.01). It is remarkable that major vascular alterations were prevented and lifespan normalized in HGPSrev mice when progerin suppression and lamin A restoration were restricted to vascular smooth muscle cells and cardiomyocytes.

    Conclusions: HGPSrev mice constitute a new experimental model for advancing knowledge of HGPS. Our findings suggest that it is never too late to treat HGPS, although benefit is much more pronounced when progerin is targeted in mice with mild symptoms. Despite the broad expression pattern of progerin and its deleterious effects in many organs, restricting its suppression to vascular smooth muscle cells and cardiomyocytes is sufficient to prevent vascular disease and normalize lifespan.