Category: Science

Initial Evidence of Clinical Activity Shown with Givosiran

prescriptiondrugs_675202Abstract from Alnylam:

 Initial results from Part C, which is a randomized, double-blind, placebo-controlled (3:1, drug:placebo) study in patients with acute intermittent porphyria (AIP) experiencing recurrent attacks, showed robust and durable lowering of aminolevulinic acid (ALA) and porphobilinogen (PBG), the toxic heme intermediates that are believed to mediate porphyria symptoms and acute attacks.

As of the data transfer on November 7, 2016, there were no drug-related serious adverse events (SAEs) reported in Cohorts 1-4.  In Cohort 3, which remains blinded, one death was reported after the data transfer date due to acute pancreatitis, complicated by a pulmonary embolism; the death was considered to be unlikely related to givosiran or placebo by the investigator and the study’s Safety Review Committee.

Of note, increases in pancreatic enzymes and acute pancreatitis have been reported in the literature in patients with acute hepatic porphyria (Shen et al., Acta Neurol Taiwan, 2008;17:177-183; Shiraki et al., Nihon Rinsho, 1995;53:1479-1483).

In Cohorts 1 and 2, there were no discontinuations due to adverse events (AEs).  Possibly or definitely related AEs reported in two or more cases were injection site reactions and myalgia; all of these events were mild. There were no other clinically significant changes in vital signs, electrocardiograms, clinical laboratory parameters, or physical examination.


Natural History Study for Acute Hepatic Porphyrias

prescriptiondrugs_675202Abstract from Alnylam:

“Results from 112 patients, of which 104 have acute intermittent porphyria (AIP), showed a mean of 9.5 acute attacks reported in the prior year with severe neuropathic pain as the cardinal feature in 100% of attacks, along with other symptoms including nausea or vomiting (>80%), fatigue (77%), and weakness (79%).

Approximately 64% of patients reported experiencing porphyria symptoms between attacks, with about 46% experiencing symptoms daily.  Patients also reported a diminished quality of life and significant healthcare utilization, with a mean of 4.6 overnight hospitalizations per year (range 0-70) and a mean hospital stay duration of 6.6 days (range 1-60).

Of the attacks reported on study, approximately 76% of them required treatment with heme or at a healthcare facility.”

The Lasts but not the Worsts

celtic-raven-knot-little-bunny-sunshineAccording to statistics, in the US and EU carriers of acute porphyrias are about 1 on 10,000 PEOPLE.
Therefore, in the World porphyrias’ carriers are not less than 60,000, of which about 20,000 have suffered from one acute attack and at least 6,000 live with exacerbations and recurrent attacks.

The remaining 40,000 are not symptomatic, if not occasionally.

In Italy the forecast is about 6,000 carriers.
So, in a region like Lombardy should be expected 1,000 acarriers and about 500 each in Lazio, Campania and Sicily – without taking account of the Normans for increasing and Catholic persecution against ‘The Daemonhosts’ for decreasing..

And we should have in Italy not less than 500 patients suffering from recurrent crisis and in need of glucose infusions or heme medication at least once a year.

Well to remember that the World Statistics report also that diagnostic confirmation arrives AFTER 7-odd years since the first acute event (and potentially lethal), at least one heavy threated psychiatric patient is a carrier of porphyria exacerbated by wrong therapies, there is a correlation between deaths for acute abdomen or laparoscopic emergency and unrecognized porphyrias.

Do you know what this means?
That our life expectancy is directly related to the visibility and the ability to connect us to spread knowledge between doctors and adequate standards by burocracy.

Stay alive.
We are the Lasts but not the Worsts.

Mitochondrial DNA variation in the Viking age population of Norway

A PubMed study by Krzewińska M, Bjørnstad G, Skoglund P, Olason PI, Bill J, Götherström A, Hagelberg E.


The medieval Norsemen or Vikings had an important biological and cultural impact on many parts of Europe through raids, colonization and trade, from about AD 793 to 1066. To help understand the genetic affinities of the ancient Norsemen, and their genetic contribution to the gene pool of other Europeans, we analysed DNA markers in Late Iron Age skeletal remains from Norway. DNA was extracted from 80 individuals, and mitochondrial DNA polymorphisms were detected by next-generation sequencing. The sequences of 45 ancient Norwegians were verified as genuine through the identification of damage patterns characteristic of ancient DNA. The ancient Norwegians were genetically similar to previously analysed ancient Icelanders, and to present-day Shetland and Orkney Islanders, Norwegians, Swedes, Scots, English, German and French. The Viking Age population had higher frequencies of K*, U*, V* and I* haplogroups than their modern counterparts, but a lower proportion of T* and H* haplogroups. Three individuals carried haplotypes that are rare in Norway today (U5b1b1, Hg A* and an uncommon variant of H*). Our combined analyses indicate that Norse women were important agents in the overseas expansion and settlement of the Vikings, and that women from the Orkneys and Western Isles contributed to the colonization of Iceland.

© 2014 The Author(s) Published by the Royal Society. All rights reserved.

PMID:25487335    PMCID: PMC4275891   DOI:  10.1098/rstb.2013.0384

Book Review: The Seven Daughters of Eve

E Hagelberg1  – Evolutionary biologist – Department of Biology, University of Oslo

This book is clearly aimed at the punter. It may also interest students of the public understanding of science, particularly human genetics and evolution, as it deals with the types of questions about human origins and human history that fascinate the general public. Where do we come from? How are we related to each other? Are we descended from the Neanderthals? Are we connected genetically to some king or queen or other notable person? The style is lively and the book contains many anecdotes of the author’s exploits in the field of human genetics, which could appeal to lay people mystified or alienated by some of the activities of geneticists currently portrayed in the news media.


The title of the book refers to its last section, which draws on recent research in various universities using the maternally transmitted mitochondrial DNA, on the classification of living humans into maternal lineages characterized by specific shared mutations. In a paper published several years ago, Sykes and his coauthors postulated the existence of seven major mitochondrial lineages, or haplotypes, in Europe, although the number has been revised several times.